Drug delivery

  • Article
    | Open Access

    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.

    • Kerstin Johann
    • , Toszka Bohn
    •  & Christian Becker
  • Article
    | Open Access

    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.

    • Surya Shrivastava
    • , Roslyn M. Ray
    •  & Kevin V. Morris
  • Article
    | Open Access

    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.

    • Na Yu
    • , Yang Xu
    •  & Shutao Guo
  • Article
    | Open Access

    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.

    • Denise A. Cobb
    • , Nathan Smith
    •  & Benson Edagwa
  • Article
    | Open Access

    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.

    • Siyuan Yu
    • , Han Yang
    •  & Ningshao Xia
  • Article
    | Open Access

    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.

    • Yann Ehinger
    • , Ziyang Zhang
    •  & Dorit Ron
  • Article
    | Open Access

    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.

    • Liang Chen
    • , Wenxing Wang
    •  & Xiaomin Li
  • Article
    | Open Access

    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.

    • Timo W. M. De Groof
    • , Elizabeth G. Elder
    •  & Martine J. Smit
  • Article
    | Open Access

    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.

    • Zhijuan Yang
    • , Yujie Zhu
    •  & Zhuang Liu
  • Article
    | Open Access

    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.

    • Qiangzhe Zhang
    • , Julia Zhou
    •  & Liangfang Zhang
  • Article
    | Open Access

    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.

    • Xue Gong
    • , Haizhou Wang
    •  & Fuan Wang
  • Article
    | Open Access

    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.

    • Nagsen Gautam
    • , JoEllyn M. McMillan
    •  & Yazen Alnouti
  • Article
    | Open Access

    Iron gall chelate (GA-Fe) can promote oxygen reduction reactions and reactive oxygen species generation which causes chemical corrosion. Here, the authors, inspired by this phenomenon, develop a composite nanomedicine for tumour therapy constructed by loading gallate into Fe-engineered and PEGylated mesoporous silica nanocarrier, and show that it inhibits tumour growth.

    • Bowen Yang
    • , Heliang Yao
    •  & Jianlin Shi
  • Review Article
    | Open Access

    Given the early failing of therapeutic nanomedicine in the clinic the importance of understanding bio-nano interactions and biosystem parameters has gained much attention. Here, the authors review the work to date that looks at the impact of sex on the applications and outcomes of nanomedicine.

    • Mohammah Javad Hajipour
    • , Haniyeh Aghaverdi
    •  & Morteza Mahmoudi
  • Article
    | Open Access

    Small interfering RNA (siRNA) is used to regulate gene expression for therapeutic purposes, but the design of stable and efficient siRNA delivery systems is challenging. Here, the authors develop a siRNA-encapsulated and aptamer-incorporated core/shell nanoparticle for controlled siRNA delivery, with high stability, tumor-specific targeting and long circulation time.

    • Chang Xue
    • , Shuyao Hu
    •  & Zai-Sheng Wu
  • Article
    | Open Access

    Polymer-based systems are often considered a necessity for controlled drug delivery, but have well-known limitations. Here, the authors report on drug delivery implants formed solely from corticosteroid dimers, which demonstrate controlled release and overcome many of the challenges of polymer-based systems.

    • Kyle Battiston
    • , Ian Parrag
    •  & Wendy Naimark
  • Article
    | Open Access

    Celastrol might be useful in treating rheumatoid arthritis in part by inhibiting apoptosis of macrophages; however, systemic toxicity is a concern. Here the authors design celastrol-loaded nanoparticles that release a payload in response to MMP9 cleavage and show these NPs are effective at inducing apoptosis of human macrophages in vitro and a therapeutic effect with an adjuvant-induced arthritis model in rats.

    • Caifeng Deng
    • , Quan Zhang
    •  & Zhirong Zhang
  • Article
    | Open Access

    Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.

    • Shaobin Zhang
    • , Claudia Contini
    •  & Oscar Ces
  • Article
    | Open Access

    The iRGD tumor-penetrating peptide can achieve tumor specific drug delivery but whether and how it can penetrate into desmoplastic tumors is unknown. Here, the authors show that β5 integrin expression on tumor cells, mediated by CAFs-derived TGF-β, is required for iRGD penetration into the desmoplastic PDAC microenvironment and that iRGD-based combination therapy is effective in PDAC mouse models.

    • Tatiana Hurtado de Mendoza
    • , Evangeline S. Mose
    •  & Kazuki N. Sugahara
  • Perspective
    | Open Access

    Pain management is an extremely important topic both medically and socio-economically. Here the authors offer an overview of the use of degrading polymeric materials for delivery of pharmaceutical agents for pain management and offer a perspective of the future directions of the field.

    • Natasha C. Brigham
    • , Ru-Rong Ji
    •  & Matthew L. Becker
  • Article
    | Open Access

    Current strategies to boost anti-tumor immune response include the use of immune checkpoint inhibitors and bispecific T cell-engaging antibodies. Here the authors describe a versatile antibody immobilization nanoplatform that can be used to deliver different combinations of immunotherapeutics, showing therapeutic superiority in pre-clinical models.

    • Cheng-Tao Jiang
    • , Kai-Ge Chen
    •  & Jun Wang
  • Article
    | Open Access

    Nanoparticles have been used to reduce the toxicity associated with chemotherapeutic agents. Here, the authors report a Z-scheme SnS1.68-WO2.41 nanocatalyst for photocatalytic generation of oxidative holes and hydrogen molecules for drug-free therapeutic strategy.

    • Bin Zhao
    • , Yingshuai Wang
    •  & Qianjun He
  • Article
    | Open Access

    Cellular models are needed to study disease in vitro and to screen drugs for toxicity and efficacy. Here the authors develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization.

    • Andrew C. Daly
    • , Matthew D. Davidson
    •  & Jason A. Burdick
  • Article
    | Open Access

    Transdermal delivery has emerged as a preferred method of drug delivery. Here, the authors report on the application of porous polymer microneedles coupled with electroosmosis powered by enzymatic batteries for the transport of small and large molecules through the skin.

    • Shinya Kusama
    • , Kaito Sato
    •  & Matsuhiko Nishizawa
  • Article
    | Open Access

    Polymeric nanocarriers used for drug delivery are often coated by albumin in vivo influencing the therapeutic outcomes. Here, the authors engineer the surface chemistry of a nanocarrier to either stabilize or denature the structure of adsorbed albumin, resulting in evasion or clearance by macrophages.

    • Michael P. Vincent
    • , Sharan Bobbala
    •  & Evan A. Scott
  • Article
    | Open Access

    Durable response rate to anti-PD-1/PD-L1 therapy remains relatively low in patients with cancer. Here the authors show that metformin-loaded mannose-modified macrophage-derived microparticles reprogram the tumor immune microenvironment and improve responses to anti-PD-1 therapy.

    • Zhaohan Wei
    • , Xiaoqiong Zhang
    •  & Xiangliang Yang
  • Review Article
    | Open Access

    Advances made in synthesis and analytical techniques has allowed the exploration and mimicry of natural materials. Resilin-mimetics have emerged from this advance as a biomaterial with a range of potential applications. Here, the authors review the history and current research on resilin-mimetics, providing a future perspective.

    • Rajkamal Balu
    • , Naba K. Dutta
    •  & Namita Roy Choudhury
  • Article
    | Open Access

    The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent controls and reduces BTZ-related side effects.

    • Cinzia Federico
    • , Kinan Alhallak
    •  & Abdel Kareem Azab
  • Article
    | Open Access

    Removal of integrated HIV DNA remains a roadblock for HIV cure. Here, Mancuso et al. show that intravenous administration of an adeno-associated virus-based CRISPR/Cas9 gene editing construct to SIV-infected macaques results in excision of integrated proviral DNA from infected blood cells and tissues known to be viral reservoirs.

    • Pietro Mancuso
    • , Chen Chen
    •  & Kamel Khalili
  • Article
    | Open Access

    The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.

    • Jason V. Gregory
    • , Padma Kadiyala
    •  & Joerg Lahann
  • Article
    | Open Access

    Antibody-drug conjugates targeting high expression receptors can suffer from poor tumour penetration. Here, the authors use unconjugated antibody to improve the penetration of an antibody-dye conjugate in a clinical study, supporting further clinical investigation of the co-administration strategy.

    • Guolan Lu
    • , Naoki Nishio
    •  & Eben L. Rosenthal
  • Review Article
    | Open Access

    Microbot delivery devices are the latest development in attempts to overcome the systemic toxicity associated with classical chemotherapy. Here, the authors review the recent progress in the field with a focus on the clinical translation and potential of the research and give a future perspective on this topic.

    • Christine K. Schmidt
    • , Mariana Medina-Sánchez
    •  & Oliver G. Schmidt
  • Article
    | Open Access

    In this study, the authors combine an anti-viral drug and immune system inducer to treat influenza A and B viral infections in vitro and in vivo. They show that the compound outperforms zanamivir alone as it is still able to clear infection three days post infection, and it can be administered via different routes without reduced efficacy.

    • Xin Liu
    • , Boning Zhang
    •  & Philip S. Low
  • Article
    | Open Access

    Protein cages are used for encapsulation of macromolecules such as proteins and nucleic acids. Here, the authors report a strategy to encapsulate poorly soluble small molecules within porous protein cages through capsid-templated micelle formation and show that the resulting lipoprotein-like cages enhance the cellular delivery of these molecules.

    • Thomas G. W. Edwardson
    • , Stephan Tetter
    •  & Donald Hilvert
  • Article
    | Open Access

    Multivalent ligand-receptor interactions enhance binding selectivity in biological systems, and may be exploited to design synthetic systems. Here the authors demonstrate a multivalent behavior where the ability to bind the target occurs when the receptor density is within a specific range.

    • Meng Liu
    • , Azzurra Apriceno
    •  & Stefano Angioletti-Uberti
  • Article
    | Open Access

    Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here, the authors generate single-drug nanoparticles by hybridising lysomotropic detergents and the bisaminoquinoline-based autophagy inhibitor, and show their therapeutic potential as autophagy-inhibition based combination therapy.

    • Zhao Ma
    • , Jin Li
    •  & Yuanpei Li
  • Review Article
    | Open Access

    Retinoids are involved in a wide range of cellular functions; as such, delivery systems for retinoids are of significant clinical interest. Here the authors review the advances in preclinical and clinical testing regarding retinoid formulations in the context of regenerative medicine, brain, cancer, skin and immune diseases.

    • Raquel Ferreira
    • , Joseph Napoli
    •  & Lino Ferreira
  • Article
    | Open Access

    Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). Here, the authors use ratiometrically designed nanoparticles to codeliver the CDK4/6 inhibitor palbociclib and the autophagy inhibitor hydroxychloroquine, and show their synergistic therapeutic effects in mouse model of PDAC.

    • Ying Ji
    • , Xiangsheng Liu
    •  & Huan Meng