Drug delivery articles within Nature Nanotechnology

Featured

  • Article |

    Understanding how cells process nanoparticles is crucial to improve nanomedicine efficacy. Here a genome-wide screening is used to discover proteins that are involved in silica nanoparticle accumulation by cells and shows that different apolipoprotein receptors and proteoglycans mediate their internalization.

    • Daphne Montizaan
    • , Roberta Bartucci
    •  & Anna Salvati

  • Article |

    Manufacturing complexities, low yield and stability issues have hampered the clinical translation and scaling-up of immunoliposomes to meet the needs of pharmaceutical-grade products. The authors propose a one-step method of incorporating chimeric nanobodies tagged to hydrophobic linkers into liposomes, allowing targeted delivery of small-molecule anti-cancer drugs to tumours.

    • Md. Mofizur Rahman
    • , Jing Wang
    •  & Yuan Wan

  • Article
    | Open Access

    In regenerative medicine, stem-cell-derived extracellular vesicles are emerging as cell-free nanotherapeutics. Here, the authors show that coating these nanovesicles with blood proteins such as albumin improves their uptake by liver cells, offering a better treatment strategy for liver diseases.

    • Revadee Liam-Or
    • , Farid N. Faruqu
    •  & Khuloud T. Al-Jamal

  • Article |

    Insects have been shown to have the ability to detect different chemical agents. Here, the authors present a nanomaterial-assisted neuromodulation strategy to augment the chemosensory abilities of insects via photothermal effect and on-demand neurotransmitter release from cargo-loaded nanovehicles to augment natural sensory function.

    • Prashant Gupta
    • , Rishabh Chandak
    •  & Srikanth Singamaneni

  • Article |

    Proteins absorbed on nanomaterials often lose function due to denaturation. A poly(propylene sulfone) nanoparticle with site-specific dipole relaxation has been reported, which allows proteins to anchor to the nanoparticle without disrupting the hydrogen bonding or structure maintaining the protein functionality.

    • Fanfan Du
    • , Clayton H. Rische
    •  & Evan A. Scott

  • Article |

    Protein degradation is a powerful tool for a range of applications and therapies. Here, a selective autophagy receptor mimetic against mutant p53 protein is developed to substantially elevate autophagy levels and to recognize and transport mutant proteins for autophagy-mediated degradation and anticancer effect.

    • Xiaowan Huang
    • , Ziyang Cao
    •  & Yunjiao Zhang

  • Article
    | Open Access

    Insulin injections are not ideal and have an increased risk of hypoglycaemia. A preferable oral formulation based on silver sulfide quantum dots coated with a chitosan/glucose polymer is discussed, which has controlled insulin release and reduced risk of hypoglycaemia, and demonstrates applications in rodent and non-human primate models.

    • Nicholas J. Hunt
    • , Glen P. Lockwood
    •  & Victoria C. Cogger

  • News & Views |

    Organic and inorganic nanoparticles have different clearance mechanisms from the brain resulting in different biological fates and retention times.

    • Elizabeth Nance

  • Review Article |

    Nanoparticles naturally accumulate in the liver; this can be a major limitation to any therapy needing delivery to other organs or tissues. Here the authors review the reason for predominant liver uptake and explore different strategies used to target non-viral gene delivery nanoparticles to other organs and tissues.

    • Jeonghwan Kim
    • , Yulia Eygeris
    •  & Gaurav Sahay

  • Article |

    Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

    • Allen Y. Jiang
    • , Jacob Witten
    •  & Daniel G. Anderson

  • News & Views |

    A biohybrid nanoparticle formulation effectively treats rheumatoid arthritis by concurrently providing symptom relief and restoring proper immune function.

    • Ronnie H. Fang
    •  & Liangfang Zhang

  • Article |

    Nanoparticle penetration into tumours is an obstacle to cancer therapeutics. Here the authors show that the tumour vascular basement membrane constitutes a barrier that reduces nanoparticle delivery and demonstrate an immune-driven strategy to overcome the barrier, increasing nanoparticle movement into tumours.

    • Qin Wang
    • , Qirui Liang
    •  & Yucai Wang

  • Comment |

    Reducing cancer-related deaths can only happen with a better understanding of cancer biology and the development of improved, new therapeutics and delivery mechanisms. Nearly all cancer research is dependent upon the models being used, the model’s accuracy, and appropriate validation and benchmarking. Here the need for such considerations is discussed in line with the goal of the Cancer Moonshot.

    • Peter C. Searson

  • Article
    | Open Access

    A synthetic nanocarrier based on DNA origami chassis offers control over valency, orientation and spatial arrangement of antibodies for simultaneously engaging immune signalling pathways, checkpoint inhibition and targeted co-stimulation in anticancer immunotherapy in vivo.

    • Klaus F. Wagenbauer
    • , Nhi Pham
    •  & Hendrik Dietz

  • Article |

    PEGylated liposomal accumulation in inflamed regions has mainly been attributed to the enhanced permeation and retention effect. An arthritis model that chemotactically attracted myeloid cells shows that monocytes and neutrophils play an essential role in liposome delivery towards inflamed joints.

    • Joke Deprez
    • , Rein Verbeke
    •  & Ine Lentacker

  • Article |

    Optimizing the retention of drug delivery nanocarriers for improved cancer therapy has the potential to improve clinical outcomes. Here the authors screen 20 renal-clearable zwitterionic cyclodextrin-based nanocarriers for optimized biodistribution and tumour retention, demonstrating application in colorectal cancer models.

    • Min-Jun Baek
    • , Duy-Thuc Nguyen
    •  & Dae-Duk Kim

  • News & Views |

    Single blood vessel analysis by artificial intelligence (AI) reveals heterogeneous vascular permeability among different tumour types, which is leveraged in rationally designing protein nanoparticle-based drug delivery systems to achieve active trans-endothelial permeability in tumours.

    • Lutz Nuhn

  • Article |

    Systemic drug delivery to the bone marrow is limited, currently requiring high doses of drug, increasing the risk of side effects. Here, the authors report on the hitchhiking of drug nanoparticles in neutrophils using their natural homing to the bone marrow for targeted delivery, and demonstrate its application.

    • Zhenyu Luo
    • , Yichao Lu
    •  & Jian You

  • News & Views |

    Polymer-based nanomedicines have been engineered to ratiometrically deliver three different drugs to tumors, thereby bridging in vitro–in vivo correlation and producing synergistic therapeutic efficacy in multiple myeloma mouse models.

    • Alexandros Marios Sofias
    •  & Twan Lammers

  • Article |

    Using genetically tailored protein-based nanoprobes and taking advantage of image-segmentation-based machine learning, a high-throughput assessment of vascular permeability of individual blood vessels in 32 different tumours is quantified. These insights are valuable in developing personalized anticancer nanomedicine therapeutics and strategies modulating vascular permeability to treat tumours.

    • Mingsheng Zhu
    • , Jie Zhuang
    •  & Xinglu Huang

  • Article |

    Although nanomedicine has shown benefits with respect to soluble drug administration, whether delivery of multiple drugs within the same nanocarrier has advantages over administration of single-drug nanomedicines or combination of free drugs at the same dosage is unclear. Here we use a bottlebrush prodrug platform to show that the delivery of three drugs in a synergistic combination in animal models outperforms other combinatorial approaches for multiple myeloma therapy.

    • Alexandre Detappe
    • , Hung V.-T. Nguyen
    •  & Jeremiah A. Johnson

  • Article |

    Accumulation of visceral fat, linked to adipocyte expansion and overgrowth, is the most detrimental aspect of obesity, and a major cause of obesity comorbidities. We develop a cationic nanomedicine based on polyamidoamine dendrimers that specifically targets visceral fat and shrinks adipocytes, inhibiting diet-induced obesity and improving metabolic health in murine models.

    • Qianfen Wan
    • , Baoding Huang
    •  & Li Qiang

  • Article |

    Downregulation of specific proteins named scramblases might enhance tumour immunosuppression. In this paper the authors first show that the scramblase Xrk8 is overexpressed in tumour cells upon treatment with chemotherapeutics, and then develop a nanomedicine platform for co-delivery of a cancer prodrug and an siRNA directed against the Xrk8 gene, showing therapeutic effect and enhanced immune response in animal tumour models.

    • Yuang Chen
    • , Yixian Huang
    •  & Song Li

  • Article |

    Activation of the stimulator of interferon genes (STING) can induce immunity in various cancer therapies, but delivery of STING agonists to tumours is challenging. Now a metal-based polymeric nanoparticle delivers STING agonists to tumours upon disruption of endothelial cells in tumour vasculature and targets tumour-associated macrophages, eliciting anti-tumour immune response in hard-to-treat cancer models.

    • Kaiting Yang
    • , Wenbo Han
    •  & Ralph R. Weichselbaum

  • Article |

    While neutrophils are the first line of defence against infections and inflammation, their unrestricted recruitment and constant activation might result in prolonged inflammation and sharpening of specific pathological conditions. Here the authors develop a strategy to specifically target activated, pro-inflammatory neutrophils and neutrophil–platelet complexes to deliver therapeutics in the context of a murine model of venous thrombosis.

    • Michelle A. Cruz
    • , Dillon Bohinc
    •  & Evi X. Stavrou

  • Article |

    Nicotinamide adenine dinucleotide (NAD+) is an immune modulator that was suggested as a potential treatment for sepsis, but its in vivo benefits are contradictory and its low bioavailability as a free drug hampers potential clinical translation. Here the authors show that using a lipid-coated nanoparticle to deliver NAD+ to the cell cytosol can effectively replenish the intracellular content of NAD+ and reduce the extent of the inflammatory response in mouse models of sepsis.

    • Mingzhou Ye
    • , Yi Zhao
    •  & Shaoqin Gong

  • Article |

    Activation of the STING pathway in antigen-presenting cells has been proposed as a strategy to stimulate the adaptive immune response against tumours, but its clinical application is hampered by the instability, low specificity and low cytosolic entry of natural STING agonists. Here the authors present a platform for targeted ultrasound-mediated cytosolic delivery of STING agonists that shows efficacy in different animal tumour models and improves the response to checkpoint blockade therapies.

    • Xuefeng Li
    • , Sina Khorsandi
    •  & Jacques Lux

  • Article |

    In vivo delivery of the CRISPR/Cas system is a promising cancer therapy approach, but its efficacy is hampered by low penetrability of nanoparticles in the stiff tumour tissue. Here the authors use dendrimer lipid nanoparticles to couple PD-L1 gene editing with knockdown of FAK, a protein involved in cell adhesion, showing that modulation of the mechanical properties of tumour cells leads to enhanced gene editing and tumour growth inhibition in four different animal models.

    • Di Zhang
    • , Guoxun Wang
    •  & Daniel J. Siegwart

  • News & Views |

    A preclinical study reports a platform for the generation of dendritic cell-derived nanovesicles with enhanced immunostimulatory function, which demonstrate promising antitumoural activity in mouse models and might overcome some of the shortcomings of early-generation dendritic cell nanovaccines.

    • Yahya Mohammadzadeh
    •  & Michele De Palma

  • Article |

    Orally delivered rapamycin is an immunosuppressant that inhibits islet graft rejection in patients treated for type 1 diabetes, but it suffers from poor bioavailability, inconsistent cellular distribution and adverse reactions. Here the authors show that subcutaneous delivery of rapamycin using a polymersome platform allows for control of the drug’s biodistribution and activity on specific immune cells, which changes its mechanism of action from immunosuppression to tolerance, reduces side effects and enhances anti-inflammatory efficacy.

    • Jacqueline A. Burke
    • , Xiaomin Zhang
    •  & Evan A. Scott

  • Article |

    Malignant pleural effusion (MPE) is the terminal stage of cancer and the current standard of care for MPE is largely palliative. Here the authors design a liposomal nanoparticle loaded with cyclic dinucleotide for targeted activation of STING signalling in macrophages and dendritic cells and show that, on intrapleural administration, the nanoparticle effectively mitigates the immune cold MPE and significantly augments the checkpoint blockade immunotherapy in a mouse MPE model and clinical patients’ samples.

    • Yang Liu
    • , Lulu Wang
    •  & Dawen Zhao

  • News & Views |

    Supramolecular arrangement of proteins provides nanoparticles with neutrophil tropism via complement opsonization during an acute inflammation, enabling diagnosis and treatment of acute lung injury.

    • Jeonghwan Kim
    •  & Gaurav Sahay

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