Drug delivery articles within Nature Communications

Kasiewicz et al. describe a structure-guided rational design approach to optimize a new GalNAc-Lipid nanoparticle that enables delivery of a base editing therapy in both low-density lipoprotein receptor-deficient and wild-type nonclinical models.

In NAFLD, high levels of fatty acids in the liver impair lysosomal acidification. Here, the authors report the synthesis of novel biodegradable acid-activated acidifying nanoparticles that re-acidify lysosomes, restore autophagy, and reverse fasting hyperglycemia and hepatic steatosis in fat mice.

Sustained drug delivery is critical for patient adherence to chronic disease treatments. Here the authors apply machine learning to engineer multifunctional peptides with high melanin binding, high cell-penetration, and low cytotoxicity, enhancing the duration and efficacy of peptide-drug conjugates for sustained ocular delivery.

TRPV1 has been associated with proliferation and survival of tumors, and can be activated by heat and other stimuli. Here, the authors block TRPV1 using photothermal nanoparticles encapsulating a TRPV1 antagonist in different cancer types, which can enhance thermo-immunotherapy in pancreatic cancer models.

Platelet-neutrophil aggregates are a hallmark of thromboinflamation. Here, the authors use cargo-free particles to block platelet-neutrophil aggregates’ vascular wall adhesion, which could become an effective thromboinflammation therapy, regardless of disease cause.

Controlled delivery of small molecule therapeutics is challenging. Here the authors report a simple and effective aptamer-based depot system where the formation of aptamer/drug complexes leads to sustained release, and using this approach demonstrate improved in vivo delivery of channel blockers.

Autologous skin flap transplantation is a common method to repair complex soft tissue defects. Here the authors develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery, just improving the incidence of distal necrosis of the flap and reducing long-term functional loss.

Ebrahimi and Samanta review the key advances in the chemical and structural modification of proteins that have enabled their rise as indispensable tools in medicine and outline emerging protein engineering strategies that can potentially unlock structures with improved therapeutic properties.

Bioluminescent imaging of bacteria in vivo generally requires the use of engineered bacteria. Here the authors take advantage of bacteria specific ATP-binding cassette sugar transporters to enable selective delivery of bioluminescent nanoprobes into bacteria for visualisation, including in deep tissues.

Intratumoral abundance of chemokines, such as CXCL9, is an important driver of T cell infiltration in tumors. Here the authors describe the design of a tumor-specific expression strategy to drive secretion of CXCL9 and an anti-PD-L1 scFv (αPD-L1) in the tumor microenvironment, promoting T cell recruitment and anti-tumor immune response in preclinical cancer models.

Boron neutron capture therapy (BNCT) is a type of radiotherapy that induces cell damage through a localized nuclear reaction. Here the authors describe the design of a carborane-based covalent organic framework as a boron capsule loaded with immune adjuvants for concurrent BNCT and immunotherapy, promoting anti-tumour immune responses in preclinical cancer models.

Nanomedicine is important in cancer therapy, but loading, drug release, and therapeutic effectiveness issues limit the translation to the clinic. Here, authors report a full-API nanodrug with an ideal API content and pH-responsive release for continuous spatiotemporal cancer therapy based on PpIX-heme-CO/Fe²⁺/BV-BR metabolic pathway.

Treating acute disease like anaphylaxis is challenging due to the inability to administer therapeutics in a timely manner and regulate pharmacokinetics precisely within a short time window. Here the authors develop active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management.

Manipulating molecular self-assembly and disassembly in vivo may permit temporal control of drug delivery and release. Here, the authors report a fluorogenic cisplatin prodrug for cancer theranostics by leveraging stimuli-triggered in situ self-assembly and intracellular disassembly processes.

In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques.

Glioblastoma (GBM) is characterized by local and systemic immunosuppression, showing limited responses to immunotherapies. Here the authors describe the design of a nanoplatform composed of the lymphopenia alleviating agent cannabidiol and the lymphocyte recruiting cytokine LIGHT, promoting anti-tumor immune responses in GBM preclinical models.

Gadolinium-neutron capture therapy (Gd-NCT) in glioblastoma shows promise but is limited by toxicity and short-half life in the brain. Here, the authors present a magnetised stem cell-nanoparticle system to facilitate brain penetrance of Gd-NCT and demonstrate its utility in an orthotopic rat glioblastoma model.

Protein corona formation on nanoparticles and the resultant effects on cellular interactions is well documented, where less is known about the fate of the corona in the cell. Here, the authors track the protein corona and nanoparticles in cells and describe the separation and different processing within different cellular compartments.

Wearable transdermal iontophoresis offers advantages for patient-comfort when deploying epidermal diseases treatments but current self-powered iontophoresis based on energy harvesters is limited in the support of efficient long-term operation therapeutic administration. Here, the authors propose a simplified wearable iontophoresis patch with a built-in Mg battery for efficient and controllable transdermal delivery.

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.

Gene delivery to fibroblasts for liver fibrosis treatment remains challenging. Here the authors develop a combinatorial library of ligand-tethered lipidoids via a modular synthetic method and adopt a 2-round screening strategy to identify lipidoids for potent and selective gene delivery to fibroblasts.

Artificial organelles can potentially be used support cellular functions, but there is a trade-off between cellular uptake and cellular retention. Here, the authors report the dynamic assembly of DNA-ceria-based artificial peroxisomes in cells, and show they can be used to reduce intracellular ROS.

The probiotic Lactococcus lactis has been used for the delivery of therapeutic molecules. Here the authors engineer Lactococcus lactis to express a fusion protein of Flt3L and OX40 ligand, eliciting anti-tumor immune response in preclinical cancer models.

Here, authors show that precise integration of an rAAV vector into a chromosomal target locus results in expression of a self-cleaving guide RNA. This recombination event creates genetic resistance to a hepatotoxic compound and enables in vivo expansion of gene-edited hepatocytes using a selection drug.

While homodimeric prodrug assemblies can improve drug loading and limit toxicity in cancer therapy, bioactivation within the target site is limited. Here, the authors introduce a hybrid chalcogen bond linker to a docetaxel dimeric prodrug nanoassembly and demonstrate its improved selfassembly, redox-responsivity and antitumor efficacy.

There is still an unmet need for effective and safe drugs to treat deep vein thrombosis during pregnancy, a life-threatening condition for the mother and fetus. Here, the authors show that engineered multifunctional nanoparticles can site-specifically dissolve thrombi and reverse deep vein thrombosis-mediated intrauterine growth restriction and delayed development of fetuses in pregnant rats.

Antibacterial materials often suffer from issues around safety and application in complex in vivo environments. Here the authors report on the conjugation of electro-driven catalytic Pd-Pt nanosheets on ginger-derived extracellular vesicles for bacterial uptake and synergistic antibacterial therapy.

Liposomes are widely used in pharmaceuticals yet trade-offs between uniform size and mass production, limit production and application. Here, the authors report on the design of a microfluidic vortex focusing microfluidic technique which can mass produce liposomes with controlled size and low variability.

Achieving the delivery of drugs into the centre of solid tumours is a challenge due to the tumour micro-environment. Here, the authors propose a system for using the rapid release of large quantities of drug inside tumour microcapillaries for the gradient-driven diffusion of drugs into solid tumours.

The use of epidermal growth factor for wound healing is limited by transdermal permeability, reduction, and receptor desensitization. Here the authors develop a microneedle-based self-powered transcutaneous electrical stimulation system to overcome these challenges.

Skeletal progenitors provide a reservoir for bone-forming osteoblasts. However, the major energy source for their osteogenesis remains unresolved. Here, the authors demonstrate that ESCIT-mediated regulation of mitochondrial metabolism is required for osteogenesis.

Effective drug accumulation in deep glioblastoma multiforme (GBM) lesions remains challenging due to the blood brain barrier. Here, the authors develop a biomimetic nanogel system activated by near infrared irradiation and show high efficacy in orthotopic GBM and GBM stem cells-bearing mouse models.

Displaying the correct surface functionality at the right time is important for efficient drug delivery. Here, the authors report on the pH-responsive, sequential presentation of cell-penetrating peptide and liver-targeting moiety designed to improve intestinal absorption and liver targeting and demonstrate this with insulin delivery in vivo.

Natural buffer molecules ensure the controlled and precise delivery of specific molecules in biology. Here, the authors replicate the natural buffer systems using aptamers with controlled binding efficiency to control and maintain the levels of free drugs both in vitro and in vivo.

Regulating reactive oxygen species and inflammation are important for treating atherosclerosis. Here, the authors create a cell membrane coated zoledronic acid ceria nanocomposite loaded with probucol for synergistic drug and scavenging nanozyme treatment of atherosclerosis demonstrating application in vivo.

The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.

Fibrodysplasia ossificans progressiva is an ultra-rare genetic disorder with progressive heterotopic ossification. Yang et al develop different gene therapy approaches and show their efficacy in mouse models and in human induced pluripotent stem cells.

The development of photochromic systems is an important and growing area of research, in particular for bioactive molecular photoswitches. Here, the authors report on photopharmacological antimitotic agents, operational under visible light, based on a peptide-derived hemipiperazine photochrome.

Targeted nanoparticle delivery to sites of interest is important for targeted therapeutics. Here, the authors improve the targeting efficiency of antibodies on nanoparticles using a monobody adapter to correctly orientate the antibody to preserve targeting function and demonstrate application in targeting the vascular endothelium of human kidneys.

Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.

Hydrogenation is a treatment for chronic inflammation caused by high glucose levels in diabetic ulcers, However, current therapies have limitations. Here, the authors report on the creation of a visible light photocatalytic agent which depletes glucose in the wound and generates hydrogen to aid in diabetic wound healing.

Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics but assessing the mRNA packaging characteristics in LNPs is challenging. Here, the authors report that mRNA and lipid contents in LNP formulations can be quantitatively examined by multi-laser cylindrical illumination confocal spectroscopy at the single-nanoparticle level.

Technologies for monitoring electrophysiological effects of drugs in behaving animals have limitations. Here the authors report a wireless neural probe system with drug delivery capability for real-time monitoring of drug effects.

GTP-triggered release from drug carriers has huge potential in cancer therapy but current carriers suffers from off target release due to ATP also acting as a trigger. Here, the authors report on the development of a microtubule capsule which is engineered to be responsive to only GTP not ATP and demonstrate targeted drug delivery.

Different blood-brain barrier permeable systems, such as bacteria loaded with chemotherapy, have been proposed to treat glioblastoma. Here, the authors generate bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles to eliminate bacteria-infected glioblastoma cells and induce an anti-tumour immune response upon photothermal therapy.

Non-adherence to anti-tubercular therapy Mycobacterium tuberculosis infection can lead to treatment failure and even the development of drug resistance. In this work, the authors develop a long-acting delivery system of the anti-tuberculosis drug rifabutin and assess translational potential in vivo.

Combined immune checkpoint blockade (ICB) and photodynamic therapies have huge potential but suffer from possible damage of the antibodies. Here, the authors create a ROS-responsive hydrogel that protects the ICB antibodies and allows for sustained co-delivery and demonstrate restrained regrowth of tumours in vivo.

Biomimetic materials are of interest but can often suffer from limitations caused by the non-native linkages used. Here, the authors report on the creation of amino acid constructed polyureas which can self-assemble into vesicles and nanotubes with aggregation induced fluorescence and the potential for drug delivery applications.

Molecular chaperones play an important part in protein folding and delivery in nature. Here, the authors report on the creation of a synthetic chaperone to control the folding of therapeutic peptides from random coil to alpha helix and demonstrate enhanced therapeutic potential in an in vivo tumour model.