Bioengineering has long been inspired by nature, primarily at the macroscale1,2,3,4. The development of powerful structure elucidation techniques5,6 has further enabled the engineering and design of materials at the nanoscale, aiming at atomic precision7,8,9. Given the abundance of nanostructures in biology10,11, nanoengineering naturally enters the realm of biomimicry of natural nanoscale systems10,12,13,14. As exemplified by nacre-like nanocomposites, bioinspired nanostructures have become a driver for progress in multiple materials and devices, enabling various energy technologies15,16,17 and inspiring the rapid development of skin-like electronics. The key strategies in the design of bioinspired materials are broad utilization of the universal ability of nanoparticles to self-organize18,19 and versatile combination of nanoscale biological species, inorganic nanoparticles and abiological macromolecules20,21,22. For these reasons, device fabrication and technological translation have been drastically accelerated owing to simplified processability23,24,25, which involved the spontaneous emergence of multiple scales of organization, starting from molecular interactions26,27 and developing into complex nanoscale, microscale and macroscale patterns with various levels of complexity28,29. Bioinspired nanomaterials could thus mimic, refine and advance the variety of materials engineered by nature30,31,32.

The majority of biomolecules and their assemblies (for example, proteins and DNA) have a basic and common geometrical feature: chirality, also known as mirror dissymmetry33. Chirality is defined as the geometrical property of an object whose mirror image cannot be brought to coincide with itself34,35,36,37,38 (Box 1). Chiral objects or ensembles of objects must also not contain any improper rotation axes, such as reflection planes and inversion centres36. Unlike macroscopic systems (for example, hands), direct evaluation of the mirror asymmetry of shapes in biomolecules is not straightforward owing to their dynamic and complex structure38, as well as the limited spatial resolution of imaging systems. Albeit imperfect, circular dichroism spectroscopy—that is, the difference in the extinction of left and right circularly polarized light (CPL)39—is often used to assess the chirality of chemical and biological systems, for example to evaluate the secondary structure, folding and binding of proteins40.

Chirality, which is present across all size scales in nature, leads to biological, chemical and physical properties that may be influenced by circularly polarized electromagnetic fields41,42. For example, chiral light and surface catalytic activity have been proposed as the symmetry-related underlying causes of homochirality in the origin of life43. Therefore, chirality can be considered as a foundational bioinspired principle for engineering44,45, for example to design biosensors46, or to realize a negative refraction index47 at selected regions of the electromagnetic spectrum in chiral inorganic nanomaterials48, which demands intense optical activity in conjunction with a high degree of transparency49.

Bioinspired chiral nanomaterials are ideal for bio-physico-chemical applications, such as sensing and catalysis, in which selectivity and specificity arise as differentiating elements in comparison with non-chiral nanomaterials50,51,52,53; however, the mechanisms underlying chirality transfer processes in the preparation of inorganic nanomaterials with inherent chirality, from molecular to macroscale levels, are not sufficiently understood. Therefore, it is crucial to extract and unify lessons from biological examples of chirality transfer and determine how these criteria may guide the design of chiral inorganic nanomaterials.

In this Review, we highlight the mechanisms underlying the generation of chirality in biology, and discuss synthetic principles of bioinspired chiral inorganic nanomaterials, excluding (bio)organic–inorganic hybrid systems (for example, self-assembled nanostructures). We describe hierarchical multiscale chirality in biological systems (for example, cytoskeleton hypothesis and chirality in biominerals), and analyse the most abundant chirality transfer mechanisms in biology, including enantioselective interaction between surfaces and chiral molecules, template-induced synthesis and chirality transfer, and photon-induced chiral nanomaterials. However, as in many natural systems54, these transfer mechanisms cannot be analysed separately because a concomitance of effects is responsible for the resulting chiral morphologies, in particular for highly crystalline nanomaterials, for which template-induced and photon-induced syntheses cannot be entirely decoupled from enantioselective interactions at high Miller index surfaces. Finally, we present potential applications in photonics (for example, polarization-control, non-linear optics), sensing (enantiomer discrimination), catalysis (chemical and pharmaceutical) and biomedicine (for example, photothermal and photodynamic therapies).

Chirality in biology

Chirality exists across multiple size scales in biological entities, dictating their geometries, properties and behaviour. For example, aminoacyl-tRNA synthases, enzymes involved in the selection of amino acids in protein synthesis, preferentially bind to l-amino acids by steric exclusion of d-amino acids55. Peptide elongation of d-amino acids at the ribosomes is slow owing to the large distance between the reaction sites56, limiting the production of peptides with incorporated d-amino acids57,58. The incorporation of some d-amino acids, such as d-Asp and d-Ser, has been linked to amyloid-β peptides present in the brains of patients with Alzheimer disease59, indicating that chirality at the molecular level could extend its influence to the organism and its behaviour.

Chirality also offers survival advantage(s) for organisms. Fan-like petal arrangements of mutated Arabidopsis thaliana show left-handed chirality and clockwise twisting. The handedness of their asymmetric geometry is fixed in certain species, indicating that their chirality is genetically encoded60,61,62 (Fig. 1a,b). Although these plants normally grow straight, mutations affecting the microtubules, such as SPIRAL1, SPIRAL2 or SPIRAL3, as well as microtubule-depolymerizing drugs, such as propyzamide, cause helical growth owing to an asymmetric elongation of cells60. Spiral growth in the elongating organs is induced by the dominant-negative mutations at the tubulin intra-dimer interface. Mutation at α-tubulins 4 and 6 further decreases microtubule stability, inducing left-handed organ twisting in Arabidopsis61. Moreover, structural chirality substantially affects the mechanistic behaviour of organisms. For example, in Drosophilia, the chiral interaction of the molecular motors myosin 1D and f-actin mediates the directional twisting of cells, organs and the entire organism63. In Escherichia coli, the asymmetry in flagella movements allows the bacteria to both change direction and propel themselves forward64,65. Individuals swim by rotating their flagella anticlockwise64,66, and counteract the generated torque by rotating their cell body in the opposite direction. A combination of wall effects, flow effects and flow–wall coupling also allows bacteria to orient themselves and swim in a stable fashion67. Near a surface, these effects cause flagella to rotate clockwise68, leading to a tumbling motion of E. coli64,65.

Fig. 1: Chirality in biology.
figure 1

a, The cotyledons and first leaves of the SPIRAL2 mutant of Arabidopsis thaliana show counter-clockwise rotation60. b, Flowers of the SPIRAL2 mutant of A. thaliana also show counter-clockwise rotation60. c, The exoskeleton of Chrysina gloriosa is green under left-handed circularly polarized light (CPL), but gold under right-handed CPL42. d, The tail of the male Odontodactylus cultrifer shrimp appears differently saturated under left and right CPL. The eye of these mantis shrimps are able to adjust pitch, yaw and torsional rotation. Torsional rotation allows the shrimp to align its eyes with the polarization of incident light74,75. e, Hierarchical chirality in a plant tendril. Sugar is the building block of cellulose, which is formed into chiral microfibrils that transfer their chirality to the entire cell, cell bundles and the helical tendrils of Luffa acutangular82. f, The formation of dextral (right-handed) or sinistral (left-handed) forms in Lymnaea stagnalis is determined by the conformation of the cells in the snail embryo83. g, Chirality is transferred upwards from aragonite crystals to helical fibres, which stack parallel or transverse to each other to form a pteropod shell88,89,90. h, Chiral diversity of foraminifera skeletons. Clockwise rotation is found in animals living in high-temperate regions or tropical oceans, and counter-clockwise rotation is found in animals living in the Arctic and Antarctic oceans91,92. i, Coccolithophore skeletons show clockwise and counter-clockwise rotation88. Parts a and b adapted from ref. 60, CC BY 4.0 ( Part c is from Sharma, V., Crne, M., Park, J. O. & Srinivasarao, M. Structural origin of circularly polarized iridescence in jeweled beetles. Science 325, 449–451 (2009). Reprinted with permission from AAAS. Part d, image courtesy of Christine Huffard. Part d adapted with permission from ref. 74, Elsevier. Part d adapted from ref. 75, Springer Nature Limited. Part e adapted from ref. 82, Springer Nature Limited. Part f adapted with permission from ref. 83, Elsevier. Part g adapted with permission from ref. 235, Elsevier. Part g adapted from ref. 86, Springer Nature Limited. Part g reprinted from ref. 90, Springer Nature Limited. Part g adapted with permission from ref. 89, Wiley. Part h adapted with permission from ref. 91, Elsevier. Part h reprinted with permission from ref. 92, the Geological Society. Part i adapted with permission from ref. 236, Ocean Drilling Program.

The light polarization effects of chiral structures can also provide proliferation advantages. For example, the beetle Chrysina gloriosa shows different iridescence colours under unpolarized light and with either left or right-polarized light (Fig. 1c). The exoskeleton of C. gloriosa possesses hexagonally patterned cellular structures, with each cell containing a chiral nematic liquid crystal-like conical peak surrounded by nested arcs. Although each layer is organized along a single direction, the stacked layers form a helical Bouligand structure42. With such an exoskeleton, C. gloriosa selectively reflects left CPL to exhibit a bright metallic green colour that dims upon irradiation of light with right circular polarization42,69. Interestingly, C. gloriosa can visually differentiate reflected polarized light as a method of communication70. Similar Bouligand structures are found in many other chitinous exoskeletons71,72, for example in the mantis shrimp shell73. The circular polarization vision of stomatopod crustaceans or the mantis shrimp illustrates how organisms differentiate and use polarization-dependent optical properties. The eyes of stomatopods have high degrees of rotational freedom. By torsional rotation of their eyes, orthogonally arranged stacked layers of retinular cells in the rhabdom differentiate the polarization state of light. Furthermore, differentiating the iridescence of the telson keel under polarized light is a sex-specific behaviour; here, reflection of CPL is only observable in males (Fig. 1d). The ability to detect and analyse CPL is suggested to mediate mate signalling and to enhance contrast in turbid environments74,75. Bones76, the dermal armour of Arapaima gigas77, and Pollia condensata fruits78 also contain chiral nanostructures to improve mechanical properties.

To mimic and exploit chiral nanostructures of plants, animals and inorganic tissues for the design of nanomaterials, their evolutionary mechanism needs to be understood. The formation of asymmetry at the macroscale is often a result of chirality transfer from small to large scales, for which the nanoscale plays a crucial role79. In nature, the generation of chirality is based on hierarchy, with chiral superstructures displaying chirality at the molecular, nanoscale, microscale and macroscale. For example, the tendrils of climbing plants show helical growth by attaching their aerial axial organs to the nearby support for vertical growth and enhanced exposure to sunlight80,81. Similarly, chirality in towel gourds is hierarchical, spanning over at least six length scales from the molecular to the macroscopic level. At the molecular level, cellulose is made of chiral sugar molecules. The cellulose forms stiff and helical microfibrils, which enable swelling and deswelling of tendrils in water, resulting in a change of the fibril helical angle, which causes a torque on the cross section of the cells, forcing them to also take on a helical shape. Microscale bundles of chiral cells then group together to form the macroscopic helices of the towel gourd82 (Fig. 1e). Hierarchical chirality transfer is also present in animals, for example, in Lymnaea stagnalis snails. Sinistral or dextral chirality in these organisms can already be observed at the four-cell stage, and during the third cleavage step, from the four-cell to the eight-cell stage, micromeres rotate anticlockwise and clockwise with respect to their sister macromeres. Such embryonic chirality determines the final sinistral or dextral adult snail shells, affecting their mating behaviour83,84 (Fig. 1f). Similarly, the exoskeletons of ocean pteropods, such as Limacina helicina, have thin transparent shells that consist of microstructures made of aragonite crystal nanofibres with a right-handed orientation85,86,87,88. These helical nanofibres are densely packed to form a material that is tougher and more resistant to brittle failure than a shell made of straight fibres owing to the spring response of the coils88,89,90 (Fig. 1g).

Chirality can also be transferred from organic molecules to macroscopic morphologies in inorganic materials. Although the underlying mechanisms remain to be confirmed, chirality can be transferred through molecular interactions at organic and inorganic interfaces and biological templates. For example, the calcium carbonate shell of the foraminifera Globigerina pachyderma, a single-cell marine microorganism, shows temperature-dependent handedness. The shell spirals clockwise in high-temperature and tropical regions, whereas it spirals counter-clockwise in the oceans near the Artic and the Antarctic91,92 (Fig. 1h). Here, chiral aspartic acid (Asp) molecules generate the chiral morphologies, with enantioselective interactions of l-Asp inducing counter-clockwise rotation and d-Asp inducing clockwise rotation93. Asp interacts with the surface of calcite and alters the local free energy, resulting in the propagation of crystal growth in one direction or another94. Herdmania momus shows a similar molecular interaction-based control of macroscopic biomineral chirality. This ascidian contains an endoskeleton composed of vaterite95, which is formed through addition of Asp or glutamic acid (Glu), causing a tilt of its hexagonal subunits. Addition of the d or l enantiomers of Asp and Glu leads to the hierarchical organization of the flat platelets, which grow in a right or left spiral pattern, respectively96. Coccolithophores, a group of unicellular plant plankton, produce calcite-based exoskeletons, called coccoliths, which exist in both enantiomorph forms in nature88 (Fig. 1i). The proposed chirality transfer mechanism involves a belt of chiral macromolecules surrounding the pre-existing exoskeleton during nucleation, dictating the binding sites for calcium or carbonate ions97. Furthermore, exoskeletons of the foraminifera Orbulina universa contain a primary organic sheet, composed of polysaccharides and acidic amino acids, which is produced during the initial stage of skeleton formation. Mineral growth occurs on both sides of this primary organic sheet, providing the template that guides the exoskeleton growth for O. universa98.

Chirality transfer mechanisms

Mimicking biological chirality transfer mechanisms across multiple size scales and multiple materials groups may enable precise control of the geometric and physical properties of nanomaterials. For example, amplification of chirality transfer can be initiated from a small imbalance of symmetry in chiral catalysts to organic compounds99. In turn, a small imbalance in chirality can also induce substantial changes in the morphology of inorganic materials100. Nanoscale chirality can be induced in inorganic materials by assembly-based synthesis methods, such as DNA origami, or by self-assembly of achiral nanostructures53,101,102. Alternatively, artificial chiral inorganic nanomaterials with individual structural chirality can be synthesized using biological chirality transfer mechanisms, that is, enantioselective organic–inorganic interactions and chiral template-based chiral nanostructures. Exceeding the capability of nature, chiral nanomaterials have been designed that exploit a small enantiomeric imbalance in their response to photons to induce morphological chirality in inorganic nanomaterials (Table 1).

Table 1 Chiral inorganic nanostructures from different sources of chirality

Enantioselective organic–inorganic interaction

Interactions at the organic–inorganic interface may show enantioselective behaviour, in which the molecular binding orientation, intensity or surface density might change with respect to the relative chirality of molecules and surfaces. In addition to molecular structures, inorganic crystal surfaces may feature chirality at the atomic level, with a lack of mirror symmetry perpendicular to the surface. For example, natural minerals, such as calcite, alkali feldspar and clinopyroxenes, possess enantiomorphic crystal facets103,104. Highly symmetric metal crystals are suggested to have chirality at high Miller index surfaces105,106, that is, {hkl} (h ≠ k ≠ l ≠ 0). Such surfaces possess atomically kinked sites composed of low-index crystal facets, such as {111}, {100} and {110}107,108. Atomic kink site chirality is defined by combining the rotational directionality of low-index crystal facets. In a few specific combinations of chiral crystal facets and chiral molecules, theoretical and experimental results show handedness-dependent changes in the surface orientation of chiral adsorbates on chiral crystal facets, leading to enantioselective surface interactions103,105,109,110. For example, on Ag(643) and Cu(643) surfaces, a temperature-programmed desorption study revealed enantioselective adsorption behaviour of small chiral molecules, such as 2-butanol, propylene oxide and 3-methylcyclohexanone109. Furthermore, l-glucose shows higher electro-oxidation reactivity on Pt(643)S surfaces than d-glucose. This enantioselective catalytic activity was related to the surface density of chiral atomic kink sites106. Enantioselective adsorption of chiral molecules could also reconfigure the atomic arrangement to imprint molecular chirality on inorganic surfaces. Through powder X-ray diffraction analysis of gold nanoparticles with adsorbed p-mercaptobenzoic acid, a chiral arrangement was determined for the atomic coordination at the unit-cell level111. The synthesis of cadmium telluride (CdTe) nanoparticles using l-cysteine-methyl-ester hydrochloride showed the preservation of a chiroptic response, even after replacement of chiral ligands with achiral ligands, indicating that adsorption of chiral molecules induces the irreversible development of atomic chirality112. Density functional theory simulations and corresponding Wulff thermodynamic structure reconstructions demonstrated the preferential binding of l-cysteine to Au(321) surfaces113.

Enantioselective interactions between chiral molecules and inorganic surfaces have been proposed to induce macroscopic chirality in inorganic materials. During the synthesis of calcium carbonate, the introduction of chiral amino acids, such as Asp or Glu, induces a spiralling morphology. The resulting toroidal superstructure shows counter-clockwise spiral morphology upon addition of l enantiomers and clockwise spiral morphology upon addition of d enantiomers96 (Fig. 2a). Calcium carbonate growth can be further extended using a single amino acid enantiomer, resulting in chirality switch, which is determined by the chiral interactions of constituent nanoparticles. The proposed chiral growth mechanism follows a sequential tilt of subunit structures upon addition of chiral molecules to the surface, starting from a platelet layer inclination stage and a platelet layer rotation stage. This finding provides a hypothesis to explain enantiomeric pairs in nature, despite the homochiral propensity of biological systems114. Introduction of chiral tartaric acid, malic acid and Asp during the electrochemical growth of calcite crystals also induces chiral morphologies. Here, the type of chiral molecule and its handedness control the final morphology of the calcite crystals115 (Fig. 2a).

Fig. 2: Chiral inorganic nanomaterials synthesized from enantioselective interaction.
figure 2

a, Scanning electron microscopy (SEM) images of chiral inorganic structures grown in l or d enantiomers96. Top: chiral vaterite microcrystals synthesized using l- or d-aspartic acid (Asp). Bottom: chiral calcite microcrystals synthesized using l- or d-tartaric acid115. Scale bar = 3 μm. b, Helical arrangement of atoms in a cinnabar HgS lattice along the crystallographic c axis and transmission electron microscopy (TEM) image of individual chiral nanostructures116. Scale bar = 200 nm. c, Scanning transmission electron microscopy (STEM) image and tomographic reconstruction of chiral tellurium nanoparticles. Scale bar = 100 nm. d, Morphology development of 432 helicoid nanoparticles with respect to types of input chiral molecules133. Introduction of cysteine molecules to cubic seed nanoparticles induces chiral nanoparticles with AC boundary tilting (depicted as red-coloured nanoparticles), whereas introduction of glutathione molecules to cubic seed nanoparticles leads to chiral nanoparticles with AB boundary tilting (depicted as a blue-coloured nanoparticles). e, Low-magnification and high-magnification SEM images of 432 helicoid III nanoparticles synthesized with octahedron seed nanoparticles and glutathione molecules133. High-magnification image scale bar = 100 nm. Part a adapted from ref. 96, Springer Nature Limited. Part a reprinted (adapted) with permission from Kulp, E. A. & Switzer, J. A. Electrochemical biomineralization: the deposition of calcite with chiral morphologies. J. Am. Chem. Soc. 129, 15120–15121 (2007). Copyright 2007 American Chemical Society. Part b adapted from ref. 116, Springer Nature Limited. Part c reprinted from ref. 120, Springer Nature Limited. Parts d and e adapted from ref. 133, Springer Nature Limited.

In addition to chiral biomineral suprastructures, inorganic chiral nanomaterials with macroscopic chiral morphologies can be synthesized in the presence of chiral biomolecules. For example, the twisted morphology of mercury sulfide (cinnabar) nanoparticles can be biased to the specific mirror asymmetric form using d- and l-penicillamine molecules attached to their surface. The primary chiral unit of the cinnabar α-HgS lattice, with a P3221 space group, shows a helical arrangement of mercury and sulfur atoms along the crystallographic c axis. Here, the strong influence of molecular chirality on the crystallographic and geometric chirality of the nanoparticles was shown by two-step epitaxial growth116 (Fig. 2b). Paramagnetic, chiral cobalt oxide (Co3O4) nanoparticle synthesis can also be based on chirality transfer from organic molecules to an inorganic crystal lattice, which causes chiral distortions. Interaction with chiral cysteine molecules generates chiral distortions in the crystal lattice of cobalt oxide, resulting in chiral phonons specific for the Co3O4 lattice117. Furthermore, the synthesis of cobalt nanoparticles using the chiral Tyr-Tyr-Cys peptide demonstrates the crucial role of the thiol group and carboxyl functional group for chirality evolution, on the basis of a 2D nuclear magnetic resonance study118. Similarly, colloidal II–VI semiconductor nanoplatelets with chiral helices can be synthesized with thiolated surface ligands119. The structure and composition of chiral molecules are key, as demonstrated in the synthesis of chiral tellurium and selenium nanoparticles. Chiral tellurium nanoparticles synthesized in the presence of chiral glutathione molecules show twisted ridges and triangular protrusions at each end of the nanoparticles. However, changes in the type of material and chiral molecules induce variations in the morphology and chiroptical response of the nanoparticles120 (Fig. 2c). A more conservative role of chiral ligands has also been proposed. Thiolated penicillamine can be used in the synthesis of chiral tellurium nanoparticles with enantiomorphic chiral space groups of P3121 and P3221 (ref. 121). Interestingly, addition of achiral mercaptopropionic acid also yields similar chiral shapes of nanoparticles with equal enantiomeric ratio. Such chirality generation is attributed to screw dislocation at low-supersaturation growth conditions, with chiral ligands promoting handedness-biased synthesis. These various paths to chirality suggest that chirality transfer from small biomolecules provides a versatile route to constructing chiral inorganic materials.

Complex chiral morphologies can be obtained by controlling the adsorption of small chiral molecules on high Miller index surfaces. Various approaches have been proposed to precisely control exposed high Miller index facets in colloidal nanosynthesis122,123, including chemical strategies. For example, seed-mediated growth, in which pre-synthesized nanoscale seeds are used to separate nucleation and growth stages, enables precise morphology control in a mild synthetic environment124,125. Here, the exposed facets in the nanoparticles and the resulting morphology are determined by the cooperative influence of thermodynamic and kinetic parameters. By balancing thermodynamic parameters, such as surface energies, adsorption energies of organic ligands and halide ions on the metal, and kinetic parameters, such as pH, reducing agents and temperature, the exposed facets can be precisely controlled126,127,128,129,130. Independent variation of reagent concentrations, such as the surfactant, seed nanoparticles, metal ion precursor and reducing agent, affects nanoparticle morphology. By controlling the reactants, rod, parallelepiped, hexagonal platelet, cube and multi-branched morphologies can be designed131. Thiol-containing organic molecules can also be used to control the morphology and exposed facets during gold nanoparticle synthesis. Using strong gold–sulfur bonding and the aromatic geometry of 4-aminothiophenol, concave rhombic dodecahedral nanoparticles can be synthesized that comprise various high-index facets, such as {331}, {221} and {533}. By tailoring the thiol surface ligands, other morphologies can be obtained, indicating the potential to further expand this synthetic methodology132.

Uniform chiral gold nanoparticles with complex shapes can be grown using thiol-containing chiral amino acids or peptides in a seed-mediated synthesis133. Chiral surfaces of high-index facets preferentially interact with a chiral molecule of specific handedness. Preferential binding of molecules to the surface promotes an uneven elongation of the facet, which induces twisting of the nanoparticle geometry. Such evolution of twisted particle geometry follows the sequential trajectory of uniform high-index facet generation, tilting of edges for chiral motif formation and construction of well-defined boundaries with increased nanoparticle size134. Viewed from (110) and (100) directions, the introduction of cysteine molecules induces A′C and AC edge tilting in opposite directions, whereas the outer edges of A′C and AC shift towards the centre of the nanoparticle to create a chiral morphology. However, viewed from (110) and (100) directions, the introduction of cysteine-containing glutathione molecules induces contraction and protrusion of outer edges and pinwheel-like rotation of inner edges133 (Fig. 2d). Owing to their 432 point group symmetry and helicoid morphology, these synthesized nanoparticles are called the 432 helicoid series. The synthesis method benefits from straightforward synthetic modifications through change of seed morphologies, chiral biomolecules and the synthetic environment133,134,135,136,137,138,139. In particular, the 432 helicoid III nanoparticles, synthesized using {111} enclosed octahedron seed nanoparticles and glutathione molecules, have a chiral morphology with four highly curved gaps in a pinwheel-like chiral motif (Fig. 2e). Therefore, the 432 helicoid III particles show strongly biased absorption of CPL, which is attributed to their high-order plasmonic modes133. This synthetic platform can also be extended to other materials, for example, for the synthesis of chiral palladium nanoparticles. Introducing cysteine molecules to palladium nanoparticle synthesis induces spiral structures on each face of the cubic nanoparticles, leading to rotational direction preference with respect to the handedness of the incorporated cysteine molecules139.

Template-induced synthesis

Biological membranes are based on the ability of surfactants to form micelles in aqueous solution and their tendency to adsorb at interfaces140, the same as lipids141. Amphiphilic molecules can also serve as templates for the structural design of inorganic nanomaterials142. By incorporating asymmetric carbon atoms in the chemical structure of surfactants143, helical micelles can be formed under specific physicochemical conditions (for example, concentration, temperature and ionic strength)144. Similarly, dissymmetric nanomaterials can be based on templates made of self-assembled chiral surfactants145. However, the availability of chiral surfactants remains limited owing to time-consuming synthesis protocols. Alternatively, commercially available chiral additives can be applied as co-surfactants to induce and tailor helicity in mixed micellar aggregates146. Chiral molecules may not be indispensable to the synthesis of chiral inorganic nanomaterials147. Self-assembly into spiral micelles can also be induced using conventional surfactants; for example, in molecularly crowded environments148, helical structures can emerge in chiral multi-shelled mesoporous carbon nanospheres with different morphologies by introducing shear flows and by adjusting the concentration and amphiphilic character of surfactants, that is, by controlling the packing parameters149 (Fig. 3a).

Fig. 3: Chiral inorganic nanomaterials synthesized by templating of worm-like helical micelles.
figure 3

a, Transmission electron microscopy (TEM) images of chiral mesoporous carbon nanospheres with right and left-handedness, prepared with spiral micelles149. b, Scanning electron microscopy (SEM) image and schematics of a structural model of chiral mesoporous silica nanoparticles151. c, TEM image (top left), central slice through the TEM tomography reconstruction (top right) and voxel projections of the reconstructed volume (bottom) of a chiral silica nanoparticle153. d, SEM images (scale bars = 100 and 50 nm) of right-handed surfactant–TiO2 fibres. TEM image (scale bar = 10 nm) (centre) shows a tube in the centre of the fibre, and the schematic shows a structural model of the surfactant–TiO2 fibre155. e, SEM images of chiral CuO nanoflowers at different synthesis times, t = 75 min (top left) and 135 min (top right), and their chiral corresponding nanopetals (bottom)156. f, Tomography reconstruction based on a tilt series of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images (top left) and a HAADF-STEM projection image (top right) (scale bar, 100 nm) of gold nanorods grown in the presence of chiral micelles; HAADF-STEM (bottom left) and energy dispersive X-ray spectroscopy (bottom centre, platinum displayed in green) tomography reconstruction and HAADF-STEM projection image (bottom right) (scale bar, 100 nm) of chiral gold nanorods coated with platinum160. g, Molecular dynamics simulations of helical micelles in solution (top); here, aggregation of surfactant (blue) in the presence of co-surfactant (red) results in chiral, worm-like micelles; molecular dynamics simulations for helical micelles adsorbed onto a gold nanorod in axial and lateral views (bottom)160. h, 3D colour-coded volume renderings of helicity maps for different chiral gold nanorods (red and blue indicate right and left-handed helical features, respectively) (scale bar = 50 nm)161. Part a reprinted from ref. 149, CC BY 4.0 ( Part b reprinted from ref. 151, Springer Nature Limited. Part c reprinted with permission from ref. 153, Wiley. Part d reprinted from ref. 155, Springer Nature Limited. Part e reprinted (adapted) with permission from Duan, Y. et al. Optically active chiral CuO “nanoflowers.” J. Am. Chem. Soc. 136, 7193–7196 (2014). Copyright 2014 American Chemical Society. Parts f and g adapted/reprinted from González-Rubio, G. et al. Micelle-directed chiral seeded growth on anisotropic gold nanocrystals. Science 368, 1472–1477 (2020). ©The Authors, some rights reserved; exclusive licensee AAAS. Part h is reprinted from ref. 161, CC BY 4.0 (

Mineralization of chiral micelles into chiral silica nanostructures results in a range of morphological features with controlled size, shape, chiral structure and helical pitch length150. This synthetic process is based on tuning the interactions at the micelle head group between a chiral anionic amino acid-based surfactant, mixed with the corresponding amino acid precursor as co-surfactant, and a small amount of silica precursors, such as cationic quaternized aminosilanes and tetraethoxylsilane derivatives, under acidic conditions151. The presence of helical micelles induces changes in the isotropic condensation and growth of mesoporous silica, thereby leading to a chiral distortion of the final rod-like nanoparticles (Fig. 3b). The resulting morphologies can be simulated by a structural model of twisted shaped rods with inner chiral channels that perfectly match the surfactant micelle organization (Fig. 3b). In addition, the combination of tartrate-based chiral anionic counter-ions, together with achiral ammonium-type surfactants, can direct the handedness of helical silica. Chiral mesoporous silica nanoparticles can also be obtained using fully achiral cationic alkyltrimethylammonium surfactants as templates152 and tetraethoxylsilane in highly concentrated solutions of ammonia153. This process relies on an entropically driven model154, in which non-chiral micelles take on a helical conformation as a consequence of strong repulsion between ammonium cations and positively charged surfactant head groups, inducing the formation of spiral silica nanoparticle morphologies with helical mesoporous channels (Fig. 3c).

Chirality can also be templated into metal oxide nanomaterials using superstructures of small molecules. For example, crystalline chiral TiO2 fibres can be synthesized by transcription and calcination of the helical structure formed by anionic amino acid-derived surfactant aggregates, combined with metal–organic titanium precursors155 (Fig. 3d). Here, chirality transfer is achieved owing to the favourable interaction between the hydrolysed titanium salt and the anionic head groups of the chiral surfactant under acidic conditions, which induces the formation of TiO2 double helical ribbons with inner tubes (Fig. 3d). Alternatively, achiral anionic surfactants (for example, sodium dodecylsulfate) can serve as structure-directing agents to synthesize chiral CuO flower-like structures using an amino alcohol as the symmetry-breaking co-surfactant, under hydrothermal conditions156 (Fig. 3e). Such microstructures are composed of nanopetals, in which layers of CuO are stacked and connected into a helical arrangement. Consequently, enantiomeric CuO microflowers with nanopetals of the opposite handedness can be synthesized in the presence of different amino alcohol enantiomers157.

The cationic surfactant cetyltrimethylammonium bromide (CTAB) can assist the seed-mediated growth of anisotropic gold nanostructures, such as nanorods158. In addition, long alcohol chains can be used as co-surfactants to control the organization at the nanoparticle–solvent interface, thereby improving reproducibility in the synthesis of highly monodisperse gold nanorods159. Such surfactant-assisted growth allows the engineering of chiral gold nanorods by relying on the templating effect of chiral micelles induced by the presence of an amino-aromatic co-surfactant with axial dissymmetry160 (Fig. 3f). Molecular dynamics simulations revealed that chiral additives induce the self-assembly of surfactants into chiral worm-like micelles, which tend to coil around gold nanorods, acting as templates for the seeded growth of chiral features (Fig. 3f). High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) tomography reconstructions of such chiral nanorods further demonstrate the presence of sharp wrinkles oriented in a radial direction, displaying tilt angles with respect to the transverse dimension. The resulting chiral templating effect, in which the enantioselective adsorption of micelles at high Miller index surfaces of gold nanorods cannot be excluded, represents an example of the combination of two concomitant chirality generation mechanisms. Interestingly, this approach also works for the synthesis of quasi-helical platinum shells on gold nanorods, as illustrated by HAADF-STEM and energy dispersive X-ray spectroscopy tomography reconstructions (Fig. 3f). The helical features in the final chiral nanoparticles can be quantified by analysing their geometrical features, based on electron tomography reconstructions of the gold nanorods (Fig. 3f), allowing the extraction of different parameters, including the inclination angle161. This template-induced synthesis approach may be further investigated by exploring new surfactants (for example, gemini surfactants162) and biological co-surfactants (for example, amyloid proteins163), to obtain metal nanoparticles in which the helical morphology of wrinkles is better defined, and parameters, such as width, depth and pitch, are finely controlled.

Photon-induced chirality in nanomaterials

Light is a desirable source of chirality for the large-scale synthesis of molecular, nanostructured and microstructured materials because of its nearly perfect enantiopurity that is difficult to attain for chemical molecules, even after multiple cycles of purification164,165. Additional advantages of CPL as a chirality inducer are the low cost of its mirror asymmetry and the simplicity of spectral tunability166. For example, chiral CdTe nanoparticles, prepared with thioglycolic acid (TGA), can be exposed to CPL, which causes photo-oxidation of Te2− and CdS, ultimately driving the replacement of Te2− with S2− ions and self-assembly of the nanoparticles into twisted ribbons167,168 (Fig. 4a). Enantiomeric excess exceeding 30% can be achieved by illumination of twisted nanoribbons with left and right-handed CPL, resulting in twisted nanoribbons with identical handedness169 (Fig. 4b). CPL irradiation drives the ion exchange of Te2− with S2− through TGA photo-oxidation. Owing to the chiral geometry of the individual nanoparticles, one enantiomer in the racemic mixture preferentially absorbs chiral light of the same handedness, resulting in the formation of nanoribbons made primarily of one ‘nano-enantiomer’169. CPL can also be used to alter the shape of chiral materials, by either increasing or reducing their asymmetry. Chiral nanoparticles made of gold, grown with left-handed or right-handed CPL, become more asymmetric when illuminated with light of the same handedness as the particle, and less asymmetric when illuminated with light of the opposite handedness170 (Fig. 4c).

Fig. 4: Photon and external field-induced chiral nanostructures.
figure 4

a, Formation of chiral cadmium tellutide (CdTe) nanostructures with light (top) and in the dark (bottom) over 72 h. Particles exposed to light form twisted ribbons, whereas particles in the dark form straight ribbons167. b, Tomographic (top) and scanning electron microscopy (SEM) (bottom) images of CdTe nanoribbons with chirality induced by illumination of left circularly polarized light (CPL) and right CPL. Scale bars = 100 nm (ref. 169). c, Growth of chiral gold nanoparticles synthesized with l-cysteine under right and left CPL. Illumination with left CPL amplifies asymmetry, whereas illumination with right CPL reduces assymetry170. d, SEM images of particles made of gold nanoprisms and l-cysteine–phenylalanine (CYP) dipeptides, and illuminated with left CPL over time. Blade-like structures grow in a spiral shape from the prism surface173. e, Plasmonic nanostructures with a gold core, deposited with PbO2 under irradiation with left and right CPL, form chiral particles. PbO2 can be reduced under UV light. SEM images show chiral (left-handed and right-handed) Au–PbO2 nanostructures. Scale bars = 100 nm (refs. 175,176). f, A solution of gold(III) chloride and citrate illuminated with left or right CPL forms nanostructures with non-obvious chirality178. Part a adapted/reprinted from Srivastava, S. et al. Light-controlled self-assembly of semiconductor nanoparticles into twisted ribbons. Science 327, 1355–1359 (2010). ©The Authors, some rights reserved; exclusive licensee AAAS. Part b adapted from ref. 169, Springer Nature Limited. Part c reprinted (adapted) with permission from Wang, H. et al. Selectively regulating the chiral morphology of amino acid-assisted chiral gold nanoparticles with circularly polarized light. ACS Appl. Mater. Interfaces 14, 3559–3567 (2022). Copyright 2022 American Chemical Society. Part d reprinted from ref. 173, Springer Nature Limited. Part e reprinted (adapted) with permission from Morisawa, K., Ishida, T. & Tatsuma, T. Photoinduced chirality switching of metal-inorganic plasmonic nanostructures. ACS Nano 14, 3603–3609 (2020). Copyright 2020 American Chemical Society. Part e reprinted (adapted) with permission from Saito, K. & Tatsuma, T. Chiral plasmonic nanostructures fabricated by circularly polarized light. Nano Lett. 18, 3209–3212 (2018). Copyright 2018 American Chemical Society. Part f reprinted (adapted) with permission from Kim, J.-Y. et al. Assembly of gold nanoparticles into chiral superstructures driven by circularly polarized light. J. Am. Chem. Soc. 141, 11739–11744 (2019). Copyright 2019 American Chemical Society.

Correspondingly, asymmetry can also be introduced into achiral shapes using CPL. Achiral gold nanoprisms made in the presence of chiral dipeptides can be grown into chiral particles under CPL. Here, light generates localized electric field hot spots, which tend to form at the edges and vertices of anisotropic plasmonic nanoparticles101,171,172. Under exposure to CPL, blade-like protrusions are formed at the nanoprism core, which further grow into a spiral pattern through the generation of hot spots at the nanoparticle corners (Fig. 4d). Although the handedness of the resulting particles originates from the dipeptide used in the synthesis, the extent of asymmetry in the resulting nanoparticles can be adjusted through the use of either left-handed CPL, right-handed CPL or linearly polarized light173. Chiral nanostructures can also be created using plasmon-induced charge separation, to grow a chiral shape from an achiral core without the addition of chiral molecules or nanoparticles166,174. For example, CPL can create chiral particles from colloidal gold nanocuboids and lead nitrate. Here, the incident light is circularly polarized, causing the formation of hot spots on specific corners of the gold cuboid cores, where growth is then driven through the oxidation of Pb2+ into PbO2. As a result, the nanoparticles acquire a chiral shape without the addition of chiral molecules166. This process can be reversed by reduction of PbO2 with UV light, resulting in a soluble form separated from the gold core. Therefore, the handedness and morphology of the particles can be modulated using light only175,176 (Fig. 4e). Computational modelling suggests that chiral structures synthesized with CPL can be smaller than their resonant wavelength, and that gold nanoparticles can be grown into homogeneous chiral particles by depositing gold through a chemical reaction driven by the hot spots177. Moreover, CPL can be used to grow chiral nanoparticles directly from metal ions in solution. In an achiral solution of gold chloride hydrate and citrate ions, CPL leads to a chemical reduction chiral nanoparticles. This light to matter chirality transfer has high efficiency for gold, with enantiomeric excess exceeding 30%178. The resulting particles are non-helical and non-tetrahedral, and thus their handedness can be determined by calculating their Osipov–Pickup–Dunmur chirality descriptor, which measures the change in positive to negative sign, when a chiral geometrical structure is reflected in a mirror178 (Fig. 4f).


The diversity of synthesis procedures and resulting properties of chiral nanostructures allow various applications, including photonics, sensing, catalysis, drug delivery and biomedicine. Although primarily explored for photonics and sensing thus far, bioinspired chiral inorganic nanomaterials may be applied for various other applications, including in biomedicine (Fig. 5).

Fig. 5: Applications of bioinspired chiral inorganic nanomaterials.
figure 5

The diversity of synthesis procedures and resulting properties of chiral nanostructures may allow applications with respect to the design of chiral nanomaterials. a, In photonics, selective modulation of optical responses can be achieved by exploiting the chirality of nanomaterials. b, In sensing, chiral nanomaterials enable the highly sensitive detection of molecular chirality. c, In biomedicine, the handedness-specific impact of chiral nanomaterials on cells and the cellular environment can be exploited for modulating cells and cellular components. d, In catalysis, selective synthesis of chiral molecules can be achieved using chiral nanomaterials. CPL, circularly polarized light.


Chiral materials differently absorb left-handed and right-handed CPL. Their chiroptical properties can be described by their g-factor, which refers to the dimensionless ratio of circular dichroism to extinction at any given wavelength. This ability to selectively absorb chiral light renders chiral particles particularly useful for photonics179. Materials with a high g-factor, and thus high chiroptical activity, can efficiently modulate the polarization of light. For example, the 432 helicoid III nanoparticles provide control over the polarization state of light, exhibiting a maximum g-factor of 0.2. By altering the size of these particles, through varying the initial concentration of seed nanoparticles, the wavelength displaying the maximum g-factor can be finely tuned. Under cross-polarized conditions and using different angles of an analyser filter, particles with different sizes enable precise modulation of visible light, generating vivid colours133. Of note, the non-linear optical response of chiral nanomaterials may be stronger than the linear response; for example, 432 helicoid III nanoparticles have non-linear g-factors of up to –1.63 (ref. 180). The strong and tunable scattering of these particles make them applicable in photonic systems, such as emitters180.

Other non-linear optical responses in chiral nanostructures include third harmonic Mie scattering on CdTe helices dispersed in liquid. Studies of the non-linear optical effects of these helices have resulted in the discovery of a new method to characterize the chiroptical properties of nanomaterials with sample volumes of less than 1 μl, which is a hundred to a thousand times smaller than what is currently required181,182. Micelle-directed chiral growth on gold nanorods results in materials with intense circular dichroism, which can be tuned by adjusting the seed conditions, such as the concentration of gold nanorod seeds in the growth solution. Here, the optical activity can be readily extended into the near-infrared (NIR) range, even reaching telecommunication wavelengths160.


The optical activity of chiral materials can also be exploited for (bio)sensing, based on changes in the peak wavelength of the circular dichroism signal183. Chiral gold or silver nanoparticles selectively aggregate in the presence of one of the enantiomers of a small molecule, thereby resulting in a colour change of the colloid184,185,186. Gold nanoparticles can also be used in conjunction with cysteine-modified nanoparticles for the detection of l- or d-cysteine. The NIR light emission of the gold nanorod–nanoparticle system is quenched in the presence of cysteine of the same enantiomer as the nanoparticle. However, such systems need to be tailored for specific analytes, limiting their versalility187.

Chiral plasmonic nanostructures, including gold, silver, magnesium and alloyed materials, can be applied for chemical sensing by exploiting their localized surface plasmon resonances188,189,190. Chiral plasmonic nanostructures greatly improve the limit of (bio)molecule detection based on circular dichroism spectroscopy, compared with colorimetric probes191, because nanoscale particles have a markedly different distance dependence for polarization rotation compared with absorption, and because plasmonic nanoparticles typically have low-noise circular dichroism spectra in the 500–800 nm spectral window192. Subtle changes in the local refractive index may induce a localized surface plasmon resonance shift193. For example, the hydrogenation of palladium nanohelices decreases the intensity of the circular dichroism signal, allowing the optical detection of hydrogen gas concentration in air189. Chiral assemblies comprising a gold shell as a core made of gold nanoparticle satellites (linked through DNA hybridization) can detect the presence of the mycotoxin ochratoxin A through changes in the intensity of the circular dichroism signal194. Gold nanorod assemblies have been used to detect attomolar levels of DNA through a polymerase chain reaction-based assembly method195. The initial concentration of DNA alters the circular dichroism signal intensity of the nanorod assemblies, and these changes can be used to determine the presence and concentration of DNA segments196.

Circular differential scanning intensity spectra can be recorded for single particles. By averaging multiple circular differential scanning intensity measurements over time, contributions to the circular differential scanning intensity from linear optical anisotropies approach zero. The ability to detect a chiroptical signal from a single plasmonic nanoparticle paves the way for the development of new types of plasmonic sensing195. Plasmonic sensors with chiral inorganic morphologies are typically synthesized by top-down approaches, such as lithography, which often require expensive, specialized equipment183,197. By limiting batch to batch variation between particles, chiral sensors could be produced with high throughput and low costs198.


The biomimetic and bioinspired aspects of chiral nanoparticles can be particularly attractive in chiral catalysis occurring on chiral supraparticle assemblies that replicate (in size, function and formation pathway) similar organelles in bacteria. Chiral assemblies of ZnS nanoparticles, stabilized with l- or d-penicillamine, catalyse the photo-oxidation of tyrosine, with preference for the same handedness as that in the nanoparticle assembly. Coupling between the different nanoparticles in the assembly induces the transfer of excited states, while protecting the ligands near the core of the assembly, thereby improving the stability of the chiral catalyst199. Chiral selectivity in inorganic nanomaterials originates from the combination of chiral atomic surfaces and a strong chiroptic response. Furthermore, nanostructured assemblies with macroscopic chiral morphologies often possess chiral atomic sites that can enantiospecifically interact with chiral molecules. For example, cysteine-induced chirality of gold nanoparticles has precise homochiral facets, which can selectively catalyse the electro-oxidation of l- and d-tryptophan200. During electro-oxidation, chiral gold nanoparticles with {\(12\phantom{\rule{ 0.25em}{0ex}}\bar{5}\phantom{\rule{ 0.25em}{0ex}}8\)}R facets promote a higher oxidation current density for l-tryptophan than for d-tryptophan. Similarly, chiral cavities generated by l- and d-3,4-dihydroxyphenylalanine on mesoporous metal structures can enantioselectively distinguish chiral molecules201. The chiral cavities serve as active sites and retain their chiral character even after removal of the molecular template. This approach can be applied for enantioselective catalysis, for example, for the electrochemical reduction of achiral phenylglycolic acid into chiral mandelic acid202.

The optical activity of chiral metal nanoparticles dictates the directionality of catalysis203. Chiral gold nanoparticle cores impart chirality dependence to the photocatalytic properties of achiral shell materials. Particles with a CdS shell show increased hydrogen evolution when illuminated with light of handedness matching that of the particle, compared with the opposite chirality or the use of linearly polarized light204. Metallic nanohelices, made from silver or copper, enantioselectively catalyse the photocyclodimerization of anthracene-2-carboxylic acid, as a result of chiroplasmonic effects at the nanohelix surface204,205.

Furthermore, chiral nanoparticles can selectively cleave DNA. CdTe nanoparticles with chiral ligands recognize and cut a specific restriction site through photonic excitation. Particles illuminated with CPL of the opposite chirality produce reactive oxygen species (ROS), including hydroxyl radicals, which oxidize the phosphodiester bond between the T and A bases in DNA. Although the efficiency of this reaction does not depend on the enantiomer of the cysteine ligand, chirality is important because the production of ROS is affected by the relative handedness of the incident light and the ligand206. Similarly, cysteine-derived, chiral carbon dots may cleave single strands of a DNA double helix by producing hydroxyl radicals. Here, the biomimetic enzyme-like function of the chiral carbon dots is realized through stronger intercalative binding of d-cysteine to DNA, compared with l-cysteine, making carbon dots synthesized with d-cysteine more efficient catalysts207.

Biomedical applications

In biomedical applications, NIR wavelengths are preferred because of their longer penetration depth through tissues208. For example, CdTe helices have tunable optical activities in NIR wavelengths, and can thus be used to modulate light for biomedical and optical computing applications181. Chiral molybdenum oxide nanoparticles can be applied for photothermal therapy, increasing light-induced heating under CPL. The strong absorption of these particles allows local heating of tumour tissue, without causing radiation damage to healthy tissue209. Gold nanobipyramids conjugated with d-Glu show enhanced bactericidal effects, compared with achiral nanoparticles or l-Glu, through the synergistic effect of multiple mechanisms, although the exact mechanisms remain to be elucidated. d-Glu can inhibit d-Glu-associated catalysis, thereby disrupting peptidoglycan biosynthesis, which is crucial for bacterial cell wall viability. In addition, physical piercing of gold nanobipyramids into the bacterial cell wall promotes leakage, further enhancing the antibacterial effect. Moreover, under NIR radiation, photothermal heating of gold nanobipyramids decreases the viability of Staphylococcus epidermidis, promoting healing in infected rat wounds210.

The intrinsic structural chirality of gold nanomaterials can also be exploited to modulate the immune system173. For example, achiral and left-handed and right-handed gold biomimetic nanoparticles elicit different immune responses in vitro and in vivo. Importantly, the intrinsic structural chirality of the nanoparticles is triggering the immune response. Binding of nanoparticles to the G-protein-coupled receptors cluster of differentiation 97 (CD97) and epidermal growth factor-like module receptor 1 (EMR1) results in endocytosis of the nanoparticle and the opening of mechanosensitive potassium-efflux channels, causing the production of inflammasomes. Although both enantiomers undergo endocytosis, the left-handed nanoparticle enantiomer shows stronger association with the receptors owing to supramolecular interactions between the curved chiral nanoparticle surface and the chiral extracellular domains (epidermal growth factor (EGF)-like segments) in both receptors. Selective blocking of the potassium-efflux channels inhibits inflammasome activation, indicating the importance of these channels in the immune response to the gold nanoparticles. Therefore, chiral nanoparticles have been explored as adjuvants for the H9N2 influenza vaccine in C57BL/6 mice. Here, left-handed nanoparticles showed 1,258-fold higher influenza-specific antibody generation, compared with right-handed nanoparticles, along with an increase of immune-related cell proliferation. Such enantiomer-dependent immune reactivity of engineered chiral inorganic nanostructures raises the possibility of immune response modulation through nanomaterials, highlighting the important role of nanoscale chirality in biological systems, in addition to the molecular (angstrom) scale chirality of l/d optical centres.


Chiral inorganic nanomaterials may be applied for various biomedical and bioengineering applications, such as sensing, photothermal and photodynamic cancer therapy, and neurodegenerative disease therapy211. The handedness-dependent physicochemical properties of chiral inorganic nanomaterials can be exploited to modulate biological components at the nanoscale, such as site-selective biocatalytic activities or immune response activation. However, clinical-level applications are yet to be developed owing to the limited understanding of the interactions between chiral inorganic surfaces and biological environments. Diversification and sophistication of chiral inorganic surfaces will increase our understanding of organic–inorganic interface dynamics and play a crucial role in their translation for biomedical applications. Chiral gold nanoparticles can manipulate immune signalling by enantiomer-dependant receptor interaction with respect to their g-factor, which is directly correlated to structural chirality173, indicating that further structural complexity in chiral nanomaterials may diversify organic–inorganic interactions to expand their applicability in biomedical applications, such as cancer immunotherapy, by modulating immune cell dynamics to alter the cancer immunity cycle212.

In enantioselective biosensing, the systematic assembly of individual chiral inorganic nanomaterials could substantially improve sensitivity and, thus, practical implementation. For example, enantioselective sensing could be achieved using freely dispersed 3D chiral inorganic nanomaterials and lithographed plasmonic structures in preclinical demonstrations to monitor avidin binding events or identify virus structures193,213. In particular, ensemble averaging of analyte detection and measurements at different relative orientations and positions102 would improve sensitivity and measurement robustness in biosensing. This could be achieved using unidirectional optical chirality induced by oriented assembly, or lattice structures made of individual chiral inorganic nanostructures214.

Importantly, exposure of chiral inorganic nanomaterials to a biological environment opens up the possibility of using handedness-dependent organic–inorganic interactions between chiral surfaces of nanomaterials and chiral molecules, so that the inorganic surface geometry may recognize conformational differences in adsorbed biological entities for target-specific biochemistry and molecular sensing. To control the interaction dynamics at the nanoscale or sub-nanoscale level, precise nanostructure surfaces are required. Therefore, characterization methods need to be optimized to precisely quantify and understand the structural chirality of individual nanomaterials, going beyond circular dichroism and electron microscopy. Although these optical and morphological analyses provide some level of understanding of the chiral system, the detailed construction and evolution mechanism of chirality may not be fully assessable. The following characterization methods may serve as analytical techniques to enumerate the mechanistic complexity of chiral inorganic nanomaterials.

Tomographic and crystallographic analysis

3D characterization tools can be used to analyse nanoparticle morphologies161,215,216,217. For example, the 3D helical morphology of gold nanorods can be analysed using electron tomography reconstructions at a single-nanoparticle level. However, the interpretation of such 3D reconstructions remains challenging and mainly relies on visual inspection. Alternatively, 3D Fourier transformations of electron tomography reconstructions allow the identification of chiral features on nanorods; however, this approach cannot provide quantitative data representative of nanorod chirality160, which would be required to gain better insight into the relation of surface morphology and chiroptic response. In addition, traditional chirality assessments, such as the Hausdorff distance and Osipov–Pickup–Dunmur chirality, can be applied for the 3D reconstruction of gold nanostructures178; through decomposing electron tomography reconstructions of a chiral shape into a combination of helices161, helical features can be spatially resolved and quantitative parameters can be extracted that can be related to chiral geometry. However, 3D reconstructions of nanostructures can take time because the computational alignment and reconstruction can take hours to days. Alternatively, acquisition and processing of data from transmission electron microscopy (TEM) tomography enables real-time 3D tomographic visualization of chiral specimens in real time, as data are collected in an electron microscope. Volumetric interpretation and calculation of chirality measures can begin in less than 10 min and a high-quality tomogram can be available within 30 min, as demonstrated for twisted bowtie assemblies218. Here, the calculation of chirality should be incorporated into the tomography software, including the open source package tomviz.

Crystallography allows the definition of exposed facets of chiral nanoparticles to assess their evolutionary pathways. For example, all possible surface orientations, including chiral surfaces, could be defined using the stereographic projection of the face-centred cubic lattice, allowing the assessment of exposed chiral surfaces in synthesized nanoparticles and analysis of their growth trajectories137. 3D characterization of the surface structure at an atomic scale would further give insight into the exact nature of chiral surfaces and micro-facets. Although atomic resolution electron tomography is possible219,220, a reliable analysis of surface facets remains challenging owing to potential artefacts, for example those related to the limited tilt range221 during acquisition. Improvement of the acquisition of tilt series and reconstruction algorithms for electron tomography might overcome such limitations222,223.

Surface-sensitive techniques in TEM, such as secondary electron imaging in scanning TEM, could reveal the presence and role of chiral facets during growth224. However, imaging surface molecules remains difficult because of their lack of contrast and sensitivity to the electron beam. Advanced TEM techniques, such as exit wave reconstruction, allow the visualization of hard–soft matter interfaces, for example metal–polymer heterojunctions225. This technique may also be applied for 3D characterization, for example, to allow direct visualization of shape-directing additives at the surface of metal nanoparticles.

Single-nanoparticle optical analysis

Single nanoparticle-level analysis of the optical response of chiral inorganic nanomaterials is crucial for the accurate quantification of chirality. Ensemble observation provides a quick and qualitative understanding of chiral systems; however, it relies on averaging the optical activity of individual chiral nanostructures. To correlate the optical spectrum of individual chiral nanostructures with their morphologies, modified dark-field transmission microscopy and single-particle chiral scatterometry can be used. These techniques can better detect the optical properties of chiral nanostructures, compared with ensemble measurements. Importantly, slight structural differences in individual chiral structures may cause large deviations in the optical spectra, hindering average ensemble optical responses226,227. Based on such measurements, a design principle has been proposed with modified synthetic conditions to construct chiral nanostructures with uniform chiral features, which allowed a significant enhancement of the g-factor from 0.2 to 0.3 (ref. 134) and 0.4 (ref. 173). Furthermore, single particle-level analysis would improve our understanding of nanomaterials dynamics in a biological environment, as well as interaction mechanisms at the molecular and nanoscale. For example, nanoparticle interactions in the body can be represented by the lock and key interaction model to analyse the effect of nanoparticle morphology and chirality on the dynamics of targeting ligand–receptor interactions, such as in immune bone marrow cells and cancer cell membranes. Single-nanoparticle orientation studies228 and multiscale structural descriptors229 can be applied to assess such lock and key interactions. Single nanoparticle-level observations of nanocatalysts have also provided insight into catalytic mechanisms230. Therefore, single nanoparticle-level analysis may improve our understanding of enantioselective interactions at the organic–inorganic interface, and the functionality of chiral inorganic nanomaterials in biological environments.

Mathematical structure and pattern analysis

New theoretical models are required to elucidate chirality transfer mechanisms and the role of chirality in the assembly and functioning of biological structures. Mathematical description and pattern analysis of self-assembled chiral components could enable direct comparison of preparation pathways of materials with nanoscale, microscale and macroscale chiral geometries. Graph theory can be applied to assess the relationship between multiscale chirality, the geometries of self-assembled structures and their functionalities28,178,231,232,233, for example to analyse the structural complexity of hierarchically organized assemblies of Au-Cys nanoplatelets28. Graph theory is applicable to any scale, thus enabling the quantitative comparison of different chiral morphologies with mirror asymmetry. In addition, an assembly structure phase diagram can be constructed to study the role of particle chirality in different assembly pathways28. Importantly, chirality and other aspects of geometry are represented as graphs resembling atomic graphs in chemistry (that is, molecules), which may be directly correlated to properties such as polarization rotation or colloidal stability. The graph theory representations and related complexity index calculations can be used as a guide for the engineering of biomimetic chiral particles and their assemblies. In practice, graph theory enables direct parametrization of atomic and nanoscale geometries, which, in turn, enables the unification of structural descriptors for biological and abiological nanostructures229. Combining graph theory descriptors with chirality measures extracted from the protein data bank and electron microscopy images would open the road for the engineering of chiral nanostructures for targeted formation of protein–nanoparticle complexes that mimic protein–protein complexes with lock and key matches of their chirality and concavity. Unified structural descriptors, including chirality measures, may also be used for training machine learning algorithms to accelerate the design of chiral nanoparticles targeting specific proteins, which currently relies on conceptual intuitive guessing or laborious Edisonian processes234.

Computational modelling

Chiral inducer molecules play an essential role in the chiral growth of crystalline nanomaterials, transferring their chirality to an inorganic lattice that may be distorted. Macro-kinetic modelling of such mechanisms requires knowledge of thermodynamic and kinetic effects of diastereomers and enantiomers. Petascale supercomputers enable computational modelling that integrates density functional theory and molecular dynamics simulations, which may allow the macro-kinetic modelling of chirality transfer processes, ultimately aiming at prediction to improve the synthesis of chiral nanomaterials, taking inspiration from biological systems.