Anionic lipids direct efficient microfluidic encapsulation of stable and functionally active proteins in lipid nanoparticles

Communications Materials, Journal Year: 2025, Volume and Issue: 6(1)

Published: Feb. 22, 2025

Language: Английский

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Optimization of Lipid Nanoparticles with Robust Efficiency for the Delivery of Protein Therapeutics to Augment Cancer Immunotherapy

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Lipid nanoparticles (LNPs) have been successful in delivering nucleic acids like siRNA and mRNA, but face challenges protein delivery due to limited encapsulation endosome escape. In this study, a family of LNPs is developed with robust high efficiency addressing the multiple barriers cytosolic by incorporating clinically approved ionizable lipids into traditional cationic LNPs. The combination enables efficient binding endosomal Optimized efficiently deliver various proteins, including antibodies, enzymes, toxins, Cas9 living cells reserved functions. Moreover, designed show serum stability during delivery, albumin adsorbed on facilitates via receptor-mediated endocytosis, enabling highly vivo. optimized successfully therapeutic proteins such as saporin interleukin-10 (IL-10) inhibit tumor growth several animal models. IL-10 loaded enhanced proliferation cytotoxicity T improved antitumor effect adoptive transferred OT-1 CD8+ melanoma. This study expands applications for biomacromolecules, LNP formulations enormous potential therapeutics treat diseases.

Language: Английский

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Multicomponent reaction-based combinatorial chemistry for accelerating the discovery of therapeutic protein and nucleic acid delivery materials

NPG Asia Materials, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 4, 2025

Language: Английский

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Chemoselective Reagents for the Traceless Bioreversible Modification of Native Proteins

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: 35(9), P. 1300 - 1308

Published: Aug. 29, 2024

Nature utilizes bioreversible post-translational modifications (PTMs) to spatiotemporally diversify protein function. Mimicking Nature's approach, chemists have developed a variety of chemoselective regents for traceless, modification native proteins. These strategies found utility in the development reversible covalent inhibitors and degraders as well synthesis functional conjugates delivery into cells. This Viewpoint provides snapshot such tools, which currently cover Cys, Ser, Thr, Lys, Asp, Glu residues N terminus. Additionally, we explore how reagents, originally by research communities with differing objectives, can be utilized synergistically. Looking forward, discuss need developing reagents labeling His, Tyr, Arg, Trp, Asn, Gln, Met C-terminus installation dynamic PTMs. Finally, broaden applicability these point out importance modular release scaffolds tunable times responsiveness multiple endogenous triggers. We anticipate that this will catalyze further technological breakthroughs rapidly evolving field.

Language: Английский

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Drug Delivery Strategies for Age-Related Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8693 - 8693

Published: Aug. 9, 2024

Drug delivery systems (DDSs) enable the controlled release of drugs in body. DDSs have attracted increasing attention for treatment various disorders, including cancer, inflammatory diseases, and age-related diseases. With recent advancements our understanding molecular mechanisms aging, new target molecules drug carriers diseases been reported. In this review, we will summarize research on identify DDS strategies

Language: Английский

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Conditional fusogenic lipid nanocarriers for cytosolic delivery of macromolecular therapeutics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Abstract Macromolecular therapeutics designed for intracellular targets must overcome systemic delivery barriers, target cell membrane impermeability, and inefficient endosomal escape. Here, we engineer a class of conditional fusogenic liposomes (C-FLIPs) that harness the catalytic activity extracellular proteases present in pathological microenvironment. This context-specific activation enables on-target fusion with cells diseased tissue, resulting cytosolic therapeutic payloads. We describe cytoplasmic three prototypic macromolecular classes: peptide degraders, cytotoxic proteins, ribonucleoprotein particles (RNPs). further develop C-FLIP to deliver granzyme B (GzmB) cytoplasm cancer vivo induce pyroptosis immunologically-inert tumors. Treatment C-FLIP/GzmB reprograms immunosuppressive tumor microenvironment synergizes checkpoint blockade result regression established tumors immunological memory. modular, non-viral, platform represents promising approach leverage protease targeted biologics.

Language: Английский

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