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| Open AccessIn vivo metallophilic self-assembly of a light-activated anticancer drug
The metallophilic interaction between cyclometalated palladium complexes can facilitate supramolecular nanostructure formation in living mice, providing a phototoxic prodrug with a long circulation time and high tumour-targeting efficiency. Upon green light irradiation, this palladium-based drug destroys solid tumours, leaving non-irradiated organs intact.
- Xue-Quan Zhou
- , Peiyuan Wang
- & Sylvestre Bonnet
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Article |
OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues
Water-soluble, cell-permeable, inert fluorescent tags called OregonFluors have been developed to withstand environmental changes while resistant towards non-specific binding with subcellular structures. These tags enable quantitative imaging of drug target availability in cells and tissues, providing a route for the future assessment of personalized therapies.
- Lei G. Wang
- , Antonio R. Montaño
- & Summer L. Gibbs
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Article |
Nanoparticle stereochemistry-dependent endocytic processing improves in vivo mRNA delivery
Stereochemistry can affect the reactivity and transport properties of small molecules; however, it is unclear whether the stereochemistry of components in a lipid nanoparticle influences its activity in vivo. Now, it has been shown that lipid nanoparticles made with a stereopure component can increase delivery of mRNA. A biological mechanism driving the effect is also proposed.
- Marine Z. C. Hatit
- , Curtis N. Dobrowolski
- & James E. Dahlman
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In Your Element |
Ionic liquids charge ahead
Choline 2-hexenoate is an ionic compound that is a liquid at room temperature, and is just one of a class of compounds that have huge potential in biomedical research and clinical applications, explains Eden E. L. Tanner.
- Eden E. L. Tanner
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News & Views |
ortho-Quinone drugs go pro
Antibody-mediated delivery of therapeutics has been primarily limited to agents containing amine, alcohol or thiol functional groups. Now, an approach has been developed to create stable and bio-reversible prodrugs that mask ortho-quinones. Drug release requires both protease activation followed by acid-assisted elimination.
- Thomas Pillow
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Article
| Open AccessControlled masking and targeted release of redox-cycling ortho-quinones via a C–C bond-cleaving 1,6-elimination
A strategy for protecting redox-active ortho-quinones, which show promise as anticancer agents but suffer from redox-cycling behaviour and systemic toxicity, has been developed. The ortho-quinones are derivatized to redox-inactive para-aminobenzyl ketols. Upon amine deprotection, an acid-promoted, self-immolative C–C bond-cleaving 1,6-elimination releases the redox-active hydroquinone. The strategy also enables conjugation to a carrier for targeted delivery of ortho-quinone species.
- Lavinia Dunsmore
- , Claudio D. Navo
- & Gonçalo J. L. Bernardes
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News & Views |
Peptides as molecular Trojan horses
Peptides are a class of versatile biomolecules that function as hormones, signalling messengers and drugs. Now, two papers report alternative approaches to tailor their chemical properties, which enables the transport of biomacromolecules into cells. These approaches could find use in a wide range of biomedical applications.
- Yuan Ping
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Article |
Tricyclic cell-penetrating peptides for efficient delivery of functional antibodies into cancer cells
Reliable intracellular delivery of antibodies is one of the grand challenges in biomedical research, with the potential to address unmet clinical needs or to enable basic research. Now, it has been shown that tricyclic peptide complexes can transport functional antibodies into the cytoplasm and nucleus of cells to specifically target intracellular proteins.
- Ole Tietz
- , Fernando Cortezon-Tamarit
- & Katherine A. Vallis
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Article |
Phase-separating peptides for direct cytosolic delivery and redox-activated release of macromolecular therapeutics
Coacervate microdroplets formed from pH- and redox-responsive peptides and self-assembled by liquid–liquid phase separation have been shown to quickly recruit macromolecular therapeutics—such as peptides, large proteins and mRNAs—and directly enter the cytosol of cells via a non-endocytic pathway. The subsequent release of therapeutic cargo is mediated by endogenic glutathione.
- Yue Sun
- , Sze Yi Lau
- & Ali Miserez
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Article |
Switching on prodrugs using radiotherapy
Prodrugs offer one route to treat cancer, but they require activation once they have been delivered to the tumour. Now, a simultaneous chemo-radiotherapy strategy has been demonstrated in mice that uses gamma or X-ray irradiation to locally activate an anticancer prodrug.
- Jin Geng
- , Yichuan Zhang
- & Mark Bradley
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News & Views |
Chemical passports to cross biological borders
The cell membrane acts as a border that restricts uptake of extracellular proteins. Now, peptide chemists have developed two new approaches for transporting functional and biologically relevant proteins across the cellular border by anchoring cyclic polyarginine peptides on the cell membrane.
- Jan Vincent V. Arafiles
- & Shiroh Futaki
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News & Views |
The liberating force of ultrasound
Sophisticated drug delivery systems are as essential to modern medicine as drugs themselves. Now, polymer mechanochemistry in sonicated solutions has been used to activate drugs in three different systems. These results offer a promising approach that can be tailored to diverse molecular structures of modern pharmaceuticals.
- Roman Boulatov
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Thesis |
A chemist’s cup of tea
Michelle Francl dips into the science of making tea.
- Michelle Francl
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Article |
A programmable polymer library that enables the construction of stimuli-responsive nanocarriers containing logic gates
A programmable polymer library that responds to external and internal stimuli has been developed and used to fabricate a series of nanocarriers for drug release. The carriers respond to disease biomarkers, triggering self-immolative motifs and leading to the site-specific release of therapeutics both in vitro and in vivo.
- Penghui Zhang
- , Di Gao
- & Weihong Tan
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Article |
Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide
A new concept for targeted drug delivery based on enrichment triggered prodrug activation has been developed. Without enrichment, the activation reaction is sluggish; however, following enrichment, the increased concentration enhances the activation reaction rate, thereby leading to the release of the payload. The same approach can be used in antibody–drug conjugate applications.
- Yueqin Zheng
- , Xingyue Ji
- & Binghe Wang
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Article |
Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery
Biomaterials that respond to precise combinations of environmental cues represent an important technology for tissue engineering and next-generation drug delivery systems. Now, a modular framework to programme material degradation following Boolean logic has been demonstrated by specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within hydrogel cross-linkers.
- Barry A. Badeau
- , Michael P. Comerford
- & Cole A. DeForest
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News & Views |
Just passing through
Intracellular protein delivery has been a major challenge in the field of cell biology for decades. Engineering such delivery is a key step in the development of protein- and antibody-based therapeutics. Now, two different approaches that enable the delivery of antibodies and antibody fragments into the cytosol have been developed.
- Macarena Sánchez-Navarro
- , Meritxell Teixidó
- & Ernest Giralt
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News & Views |
The missing link
The targeted release of bioactive molecules to diseased tissues has the potential to improve therapeutic efficacy, but not all drugs contain a free functional group that can be easily attached to an antibody. Now, a linker technology has been developed to enable the traceless release of tertiary and heteroaryl amine-containing drugs.
- Tiago Rodrigues
- & Gonçalo J. L. Bernardes
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Review Article |
Materials and methods for delivery of biological drugs
Biological drugs can offer high potency and selectivity; however, this class of therapeutics often shows poor stability upon oral administration and during subsequent circulation. This Review highlights the materials and methods used to deliver biological drugs, and discusses how these approaches can improve their pharmacokinetics.
- Alexander N. Zelikin
- , Carsten Ehrhardt
- & Anne Marie Healy
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Article |
Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody–drug conjugates
Many drugs contain tertiary and heteroaryl amines; however, these functional groups are difficult to reversibly crosslink to a carrier protein. Now, a method for conjugating anticancer and antibiotic drugs to antibodies via a quaternary ammonium salt has been developed. Cleavage of the linker results in the traceless release of the free drug and subsequent therapeutic activity.
- Leanna R. Staben
- , Stefan G. Koenig
- & Thomas H. Pillow
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Perspective |
Recent advances in the construction of antibody–drug conjugates
Antibody–drug conjugates have shown considerable promise for treating disease. However, in order to deliver their full potential, sophisticated site-specific conjugation technologies are needed. This Perspective provides an overview of the different methods used for the site-specific attachment of cytotoxic agents to antibodies.
- Vijay Chudasama
- , Antoine Maruani
- & Stephen Caddick
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News & Views |
Rise of the nanobots
Bioorthogonal catalysis provides new ways of mediating artificial transformations in living environs. Now, researchers have developed a nanodevice whose catalytic activity can be regulated by host–guest chemistry.
- Asier Unciti-Broceta
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News & Views |
Bicycling into cells
Bicyclic peptides that are cell-permeable and can inhibit an intracellular target have been developed. These peptides consist of two rings: one enables the peptide to pass through the membrane, the other can inhibit the target.
- Rob M. J. Liskamp
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News & Views |
Unleash the forces within
Liposomes are a leading drug-delivery platform in cancer chemotherapy. Now they can be used to destroy cancer cells through a method that converts chemical energy to mechanical force. These localized disruptions can cause cell death while minimizing the collateral damage to neighbouring cells.
- Weiwei Gao
- & Liangfang Zhang
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News & Views |
Relieving PEGylation
A new type of protein–polymer conjugate provides improved stability without detrimentally affecting bioactivity, and thus offers great potential for the development of new peptide-based drugs.
- Matthew C. Parrott
- & Joseph M. DeSimone
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News & Views |
Under control
Macrocyclic compounds can serve as hosts for smaller organic molecules, but precise control over the uptake and release of the guests remains challenging. Now, a host–guest system has been built that responds to the addition of metal ions, showing promise for drug-delivery applications.
- Werner M. Nau
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Article |
Loading and selective release of cargo in DNA nanotubes with longitudinal variation
Nanotubular structures made from different materials are being investigated for applications ranging from sensing to drug delivery, but controlling how they interact with ‘cargo’ molecules has proved challenging. Now, the selective uptake, precise positioning and triggered release of gold nanoparticles has been achieved with nanotubes assembled from triangular DNA building blocks.
- Pik Kwan Lo
- , Pierre Karam
- & Hanadi F. Sleiman