Biomaterials, Год журнала: 2024, Номер 313, С. 122753 - 122753
Опубликована: Авг. 20, 2024
Язык: Английский
Science, Год журнала: 2024, Номер 384(6701), С. 1196 - 1202
Опубликована: Июнь 13, 2024
In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of in cells, yielding responses. Intravenously administered gene-editing LNPs activatable tdTomato mice achieved >70% lung editing, sustaining expression >80% epithelial cells 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X mediated >95% transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function primary patient-derived bronchial equivalent to Trikafta F508del, corrected intestinal organoids and R553X nonsense mutations 50% CF mice. These findings introduce LNP-enabled tissue disease-modifying correction.
Язык: Английский
Процитировано
42
ACS Nano, Год журнала: 2024, Номер 18(11), С. 8392 - 8410
Опубликована: Март 7, 2024
Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF are often hindered NSCLCs because their limited distribution lungs and adverse on normal tissues. These challenges can be overcome delivering mRNA form to cells, a primary target VEGF-mediated pulmonary angiogenesis, suppress NSCLCs. In this study, we synthesized derivatives poly(β-amino esters) (PBAEs) prepared nanoparticles encapsulate synthetic encoding bevacizumab, an antibody used clinic. Optimization nanoparticle formulations resulted selective transfection after intravenous administration. Notably, optimized PBAE were distributed resulting secretion bevacizumab. We analyzed protein corona lung- spleen-targeting using proteomics found distinctive features potentially contributing organ-selectivity. Lastly, bevacizumab delivered lung-targeting more significantly inhibited proliferation angiogenesis than recombinant orthotopic NSCLC mouse models, supporting potential therapy its delivery through nanoparticles. Our proof-of-principle results highlight nanoparticle-mediated anticancer treatment preclinical models.
Язык: Английский
Процитировано
19
Nature Biotechnology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 14, 2025
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental deep learning pipeline comprehensively quantify the targeting nanocarriers throughout mouse body at single-cell resolution. SCP-Nano reveals tissue distribution patterns lipid nanoparticles (LNPs) after different injection routes doses as low 0.0005 mg kg-1-far below detection limits conventional imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading proteome changes, suggesting immune activation blood vessel damage. generalizes various types nanocarriers, including liposomes, polyplexes, DNA origami adeno-associated viruses (AAVs), revealing AAV2 variant transduces adipocytes body. enables comprehensive three-dimensional mapping bodies with high sensitivity should accelerate precise safe nanocarrier-based therapeutics.
Язык: Английский
Процитировано
2
Chemical Society Reviews, Год журнала: 2023, Номер 52(21), С. 7579 - 7601
Опубликована: Янв. 1, 2023
Nanotechnology has shown tremendous success in the drug delivery field for more effective and safer therapy, recently enabled clinical approval of RNA medicine, a new class therapeutics. Various nanoparticle strategies have been developed to improve systemic therapeutics, among which surface modification targeting ligands on nanoparticles widely explored 'active' specific organ or diseased tissue. Meanwhile, compelling evidence reported that organ-selective may also be achievable by administration without ligand modification. In this Review, we highlight unique set 'passive' their compositions mechanisms delivery. particular, lipid-based, polymer-based, biomimetic with tropism different organs after intravenous are summarized. The underlying (
Язык: Английский
Процитировано
29
Advanced Drug Delivery Reviews, Год журнала: 2023, Номер 203, С. 115116 - 115116
Опубликована: Окт. 21, 2023
Язык: Английский
Процитировано
28
Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 763 - 772
Опубликована: Май 17, 2024
Язык: Английский
Процитировано
15
Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 208, С. 115291 - 115291
Опубликована: Март 19, 2024
Among non-viral vectors, lipid nanovectors are considered the gold standard for delivery of RNA therapeutics. The success nanoparticles delivery, with three products approved human use, has stimulated further investigation into therapeutics different pathologies. This requires decoding pathological intracellular processes and tailoring system to target tissue cells. complexity morphology originates from assembling lipidic components, which can be elicited by various methods able drive formation desired organization. In other cases, pre-formed mixed induce self-assembly structural reorganization RNA-loaded nanoparticles. this review, most relevant their potentialities described on basis mechanism particle architecture.
Язык: Английский
Процитировано
14
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10166 - 10166
Опубликована: Сен. 22, 2024
Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges safe and effective mRNA to target tissues cells, along with controlling release from the vehicle, remains pivotal mRNA-based therapies. This review elucidates structure of LNPs, mechanism delivery, targeted LNPs various cells tissues, including leukocytes, T-cells, dendritic Kupffer hepatic endothelial extrahepatic tissues. Here, we discuss applications mRNA-LNP vaccines prevention infectious diseases treatment cancer genetic diseases. Although remain terms efficiency, specific tissue targeting, toxicity, storage stability, technology holds extensive potential
Язык: Английский
Процитировано
14
iScience, Год журнала: 2024, Номер 27(6), С. 109804 - 109804
Опубликована: Апрель 23, 2024
Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the
Язык: Английский
Процитировано
13
Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)
Опубликована: Июнь 18, 2024
Abstract Acute lung injury ( ALI ) is a common complication in patients with severe burns and has complex pathogenesis high morbidity mortality rates. A variety of drugs have been identified the clinic for treatment ALI, but they toxic side effects caused by easy degradation body distribution throughout body. In recent years, as understanding mechanism underlying improved, scholars developed new nanomaterials that can be safely effectively targeted ALI. Most these methods involve such lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles other nanomaterials, which are to reach tissues perform their functions through active targeting passive targeting, process involves cells organelles. this review, first, mechanisms pathophysiological features occurrence after burn reviewed, potential therapeutic targets summarized, existing classified, possible problems challenges discussed provide reference development
Язык: Английский
Процитировано
11