Drug delivery articles within Nature Communications

Drug delivery implants suffer from diminished release profiles due to fibrous capsule formation over time. Here, the authors use soft robotic actuation to modulate the immune response of the host to maintain drug delivery over the longer-term and to perform controlled release in vivo.

Proteolysis targeting chimeras (PROTACs) have emerged as promising cancer therapy agents but have suffered from systemic toxicity issues. Here, the authors report on the creation of polymeric PROTAC nanoparticles for tumour targeting delivery and demonstrate protein degradation in vivo, in combination with photodynamic therapy.

Targeting cancer-associated metabolism is evolving as a promising approach for cancer therapy. Here, the authors generate cancer cell-membrane encapsulated nanoparticles to induce cell cycle arrest and cytotoxicity in lactate-high cancer cells, reducing tumourigensis in glioblastoma cell-line and patient-derived models.

Bacteria in biofilms present unique metabolic conditions that limit the traditional antibiotic treatment. Here, the authors show a photodynamic therapy-activated chemotherapy potentiating the hypoxia of biofilms of methicillin-resistant Staphylococcus aureus, by developing hyaluronic acid nanoparticles functionalized with chlorin e6 and metronidazole.

Monomethyl auristatin (MMAE), also known for its radiosensitizer properties, is a common antibody drug conjugate used for cancer therapy. Here the authors show that, in combination with radiotherapy, tumor-directed antibodies or peptides conjugated to MMAE promote anti-tumor immune responses, improving response to checkpoint inhibitors in preclinical cancer models.

Tryptophan metabolism, leading to the accumulation of kynurenine (Kyn) in the tumor microenvironment, restricts anti-tumor immunity. Here the authors report the design of a hydrogel loaded with doxorubicin and Kyn-degrading kynureninase to relieve immunosuppression, showing anti-tumor responses in preclinical models.

Overproduction of efflux pumps represents an important mechanism of Klebsiella pneumonia resistance to tigecycline. Here, the authors design TPGS- and S-thanatin functionalized nanorods loaded with tigecycline to increase drug accumulation inside bacteria and overcome bacterial resistance.

The cytochrome P450 enzyme CYP1B1 is overexpressed in a variety of tumors, and is correlated with poor treatment outcomes; thus, it is desirable to develop CYP1B1 inhibitors to restore chemotherapy efficacy. Here the authors describe the creation of light-triggered CYP1B1 inhibitors as “prodrugs”, and achieve >6000-fold improvement in potency upon activation with low-energy (660 nm) light.

The current peripherally acting mu-opioid receptor antagonists present limited permeability and pharmacokinetic properties. Here, the authors develop a drug delivery approach based on AG10, which demonstrates the impact of mu-opioid receptors in the central nervous system in precipitating opioid-induced constipation.

Inflammatory bowel disease (IBD) is a complex disease that is associated with multiple genetic and environmental variables. Here the authors develop genetically engineered probiotics with selfproducing functional proteins and biofilm self-coating for safe and efficient IBD treatment in mice.

Here, using animal models, Deodhar et al. single parenteral dose of dolutegravir (DTG) prodrug nanocrystals sustains drug protein-adjusted 90% inhibitory concentration for up to a year, without injection site reactions or systemic toxicities.

Encapsulation of bioactive peptides in slow-release particles is complex and relies on organic solvents. Here, the authors absorb peptides in a polymer phase from water, creating a simple low-cost encapsulation process in a class of polymer depot.

Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment. Here, in preclinical cancer models, the authors show that PTT efficacy could be improved using tumor cell-derived microparticles that co-deliver the photosensitizer indocyanine green and a vitamin-D receptor ligand, calcipotriol, resulting in tumor extracellular matrix remodelling and ameliorated anti-tumor immune responses.

Inhibited immune response and low levels of delivery inhibit starvation cancer therapies. Here, the authors report on the co-delivery of glucose oxidase and IDO inhibitor 1-methyltryptophan using metal organic frameworks and show amplified release in response to starvation therapy along with immune modulatory effects.

Type I photodynamic therapy (PDT) sensitizers show good hypoxia tolerance but only few strategies are available for the design of purely organic Type I photosensitizers (PS). Here, the authors use biotinylation as design strategy to obtain PS-Biotin sensitizers with high efficiency for the generation of superoxide anion radicals and singlet oxygen.

Delivering the correct concentration of drugs to the correct location is a challenge in cancer therapy. Here, the authors generate a drug loaded nanoparticle that enlarges following contact with the internal tumour cell environment, resulting in the retention of the nanoparticle and loaded drugs in cancer cells.

Boron neutron capture therapy is a type of cancer therapy but is associated with insufficient boron delivery and with poor biocompatibility. Here, the authors constructed boronated lipids to generate - boronsome - and show the system can reduce tumour growth.

Increased density of tumor associated macrophages has been correlated with tumor recurrence following surgery. Here the authors design an alginate-based hydrogel encapsulating anti-PD-1-conjugated platelets and nanoparticles loaded with the macrophage-depleting CSF-1R inhibitor pexidartinib, showing inhibition of post-surgery tumor recurrence in preclinical models.

Activated hepatic stellate cells contribute towards the pathogenesis of liver fibrosis, and overexpress fibroblast activation protein. Here the authors report a targeted peptide-delivery system in which fibroblast activation protein liberates the antifibrotic peptide melittin, and demonstrate the approach attenuates fibrosis in mouse models of liver fibrosis.

Nitric oxide exerts a multitude of physiological functions and has also been exploited for anticancer therapies. Here the authors report the design of a micelle-releasing thermosensitive hydrogel system for the concomitant locoregional and lymphatic delivery of a nitric oxide donor and an anti-CTLA4 antibody, showing anti-tumor immune responses in preclinical cancer models.

Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Here the authors use a natural microalga to readily construct an oral delivery system to achieve effective radioprotection for the small intestine.

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model.

Chemical synthesis of secondary metabolites isolated from nature, and derivatives thereof, is still a paradigm of significance to drug development. Here the authors instead use bioinformatics to analyze a biosynthetic gene cluster found in the soil metagenome, and chemical synthesis of its predict product to produce lapcin, a dual topoisomerase I/II inhibitor with promising activity against cancer cell lines.

The properties of mesoporous nanomaterials have been exploited for several applications, including drug delivery and NIR-II photoacoustic imaging. Here, the authors design monodispersed semimetallic mesoporous antimony nanospheres with photothermal conversion efficiency in the second near-infrared range and drug loading capacity, showing their potential for cancer photothermal/chemo therapy.

Fluorescence probes for detecting tumours during surgery can suffer from poor accumulation and short imaging windows. Here, the author develop fluorescence probes with multiple motifs that permit enhanced circulation times, tumour targeting and use the probes to image pancreatic cancer in mice

An increasing prevalence of Gram-negative bacteria increases the interest in nanotherapies to treat antibiotic resistance. Here, the authors examine the antimicrobial activity of polymyxin-loaded cubosomes and explore a polytherapy treatment of pathogens with cubosomes in combination with polymyxin.

Antibodies targeting OX40 or CD137, two T cell costimulatory receptors, have been shown to improve antitumor immunity. Here the authors design a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in vivo, improving efficacy of anti-OX40 and anti-CD137 antibody therapy in preclinical tumor models.

RNA therapeutics have benefited significantly from decades of research on lipid nanoparticles, specifically its key component—the ionizable lipid. This comment discusses the major ionizable lipid types, and provides perspectives for future development.

The development of a drug delivery system capable of prolonged retention in the gastrointestinal tract remains a clinical challenge. Here the authors present a bio-adhesive liquid coacervate coating on the intestinal tract that acts as a flowable drug carrier, mediates the sustained release of diverse drugs, and potentially enhances therapeutic efficacy against gastrointestinal diseases.

Facioscapulohumeral muscular dystrophy is a myopathy caused by aberrant de-repression of the DUX4 gene. Here, the authors show that miR-675 inhibits DUX4 expression and protects muscles from DUX4-mediated cell death when administered to mice using AAV, and that upregulation of miR-675 via small molecules inhibits DUX4 and DUX4-associated biomarkers in myotubes derived from patients.

Lipid nanoparticle delivery of mRNA vaccines has become of particular importance, however, mRNA stability is a major concern. Here, the authors report on a study of lipid impurity mRNA interactions using reverse phase ion pair HPLC to identify reactions which render the mRNA untranslatable, reducing vaccine efficiency.

While immunotherapy is a promising cancer treatment option, durable benefits are often rare due to immune escape. Here, the authors combine epigenetic regulation with gene therapy-mediated immune checkpoint blockade and show efficient anti-tumour effects and immune response in vivo.

Bacteria-based therapy has shown promise for cancer treatment. To enhance tumor accumulation, here the authors describe the design of tumor specific aptamer-conjugated bacteria, to improve intratumor localization and enhance therapeutic efficacy.

Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.

The limited ability of cancer therapeutics in crossing the cancer cell membrane hampers their therapeutic potential. Here, the authors report Salmonella-based system for intracellular delivery of protein drugs, e.g. caspase-3, and show reduction of tumors in mouse models of breast and liver cancer.

The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.

PD-L1 is frequently expressed on the surface of cancer cells and can be excreted from cancer cells in exosomes. Here, the authors generate a nanotherapy that combines an inhibitor of exosome production and an inducer of ferroptosis, enhancing the response to immune checkpoint blockade therapy.

A strategy to control HIV-1 infection is to stably repress HIV-1 and induce “deep latency”. Here the authors show that a recombinant anti-HIV-1-1 protein can be packaged as mRNA into exosomes and delivered systemically to repress HIV-1-1 within the context of virus infected mice and achieve long term silencing of HIV-1-1 expression.

Isopropenyl ethers (IPPEs) are essential intermediates for obtaining ketal-based prodrugs and biomaterials, but traditional approaches for their synthesis are limited by poor functional group compatibility and harsh reaction conditions. Here, the authors report an organocatalytic transisopropenylation approach for IPPE synthesis in mild reaction conditions and with wide range of substrates, and use it to prepare acid-sensitive ketal-linked prodrugs and biomaterials.

Antiretroviral therapy (ART) for the treatment of HIV-1 requires life-long daily adherence to supress viral replication, and nucleoside reverse transcriptase inhibitors that are commonly used in ART have not been converted into long-acting agents. Here, the authors report two lipophilic tenofovir (TVF) ProTide nanoformulations, NM1TFV and NM2TFV, which sustain drug levels above therapeutic concentrations for two months after a single intramuscular dose in rats.

Protein delivery with cell-penetrating peptides suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting treatment success. Here the authors present an intracellular protein delivery system and demonstrate efficient delivery in vitro and therapeutic efficacy in a liver failure model in vivo.

Chronic use of mTORC1 inhibitors produces undesirable side effects in humans which limit their value for CNS disorders treatment. The authors present a binary drug strategy to protects mTORC1 activity in the periphery and show its potential utility in preclinical models of alcohol use disorder.

Despite many reports on nanoparticle-covalent organic frameworks (COF) composites, a universal strategy for the synthesis of monodisperse core-shell structured COF nanocomposites remains challenging. Here, the authors develop a strategy for interfacial growth of highly crystalline COFs on functional nanoparticles with abundant optical, electrical and magnetic properties.

Human cytomegalovirus (HCMV) can evade immune responses in latent reservoirs, which is a specific problem during transplantation. Here the authors develop a bivalent nanobody that is specific for US28, a viral receptor required by latent HCMV, and show it can partially reactivate the virus and make it susceptible to killing by T cells.

Radiofrequency ablation (RFA) is a minimally invasive tumor ablation method, however incomplete ablation and the induction of an immunosuppressive microenvironment limit its efficacy in the clinic. Here the authors design a pH-responsive lipoxidase-loaded nanoreactor, that by triggering ferroptosis and anti-tumor immunity, amplify the therapeutic benefits of RFA in preclinical models.

Phospholipase A2 (PLA2) inhibitors have been shown to be able to treat acute pancreatitis, but are toxic with systemic application. Here the authors design a nanoparticle with macrophage membrane components to carry PLA2 inhibitor to macrophages and treat pancreatitis in mice, with no evidence of toxicity.

The therapeutic application of small interfering RNA (siRNA) is challenging due to its non-specific targeting and delivery issues. Here, the authors report an endogenous micro-RNA guided and hybridisation chain reaction-promoted siRNA delivery system encapsulated in tumour-derived extracellular vesicles, with cancer-specific activation, and achieve silencing of hypoxia-related genes.

Intratumor heterogeneity in breast cancer can limit the clinical success of antibody-drug conjugates (ADCs). In this study, the authors develop dual payload Her2-ADCs that show potent anti-tumor activity against heterogeneous breast tumors in vivo.

Here, the authors provide a mechanism for an improved version of a nanoformulated myristoylated prodrug of cabotegravir (CAB), named NM2CAB, and its bioavailability, stability and pharmacokinetics in mice and rats performed in independent academic and a contracted research labs, suggesting that the extended half-life of the prodrug is not a property of enzymatic hydrolysis but rather release or dissolution of the prodrug from the nanocrystal.