Synthetic nanomaterials for spleen-specific mRNA delivery DOI

Shihong Nie,

Beiqi Yang,

Ruiying Ma

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122859 - 122859

Published: Sept. 28, 2024

Language: Английский

Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation DOI Open Access

Wencong Jia,

Ye Wu, Yujie Xie

et al.

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

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

Language: Английский

Citations

3
Targeted Delivery of mRNA with Polymer–Lipid Nanoparticles for In Vivo Base Editing DOI

Qimingxing Chen,

Yan Chang,

Xiaoyan He

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Messenger RNA (mRNA) encoding base editors, along with single guide RNAs (sgRNAs), have emerged as a promising therapeutic approach for various disorders. However, there is still insufficient exploration in achieving targeted and efficient delivery of mRNA sgRNA to multiple organs while ensuring high biocompatibility stability vivo. To address this challenge, we synthesized library 108 poly(β-amino) esters (PBAEs) by incorporating 100% hydrophobic side chains end-caps varying amines. These PBAEs were further formulated other excipients, including helper lipids, cholesterol, PEGylated form polymer–lipid nanoparticles (PLNPs). Structure–function analysis revealed that eLog P could serve predictive parameter determining the liver or lung tropism PLNPs. The end-capped monoamines was significantly higher compared those diamines. Leveraging these findings, expanded PBAE identified leading (7C8C8) efficiency outperforming current FDA-approved ionizable lipids (ALC-0315, SM-102, Dlin-MC3-DMA). LD50 empty PLNPs determined be 403.8 ± 49.46 mg/kg, indicating safety profile. Additionally, demonstrated sustained transfection activity at least 2 months when stored −20 °C after freezing 4 following lyophilization. Subsequently, vivo editing using achieved an impressive approximately 70% significant reduction protein levels exceeding 90%. Notably, synergistic effects observed through simultaneous disruption proprotein convertase subtilisin/kexin type 9 angiopoietin-like 3 genes, resulting low-density lipoprotein cholesterol over 60% several months. compelling findings provide strong support development platforms mRNA-based therapies.

Language: Английский

Citations

2
Principles of lipid nanoparticle design for mRNA delivery DOI Creative Commons
Yiran Zhang, Xinyue Zhang, Yongsheng Gao

et al.

BMEMat, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract mRNA therapeutics have significantly evolved within the life sciences, particularly in applications such as vaccines, tumor immunotherapy, protein replacement, gene editing, and monoclonal antibody therapy. To fully realize potential of drugs mitigate adverse effects, substantial vector materials been developed for delivery these pharmaceutical agents. Lipid nanoparticles (LNPs) represent most clinically advanced carriers, recognized by U.S. Food Drug Administration approved vaccines numerous clinical trials. Diverse therapeutic necessitate tailored design LNPs. Herein, we outline principles LNP delivery, focusing specifically on their effectiveness, targeting capabilities, safety profiles, nanoparticle stability. Additionally, present latest advancements mRNA‐LNP technology. This review aims to elucidate benefits systems therapeutics, providing insights into breakthroughs innovative ideas further enhancing advantages. These summaries are dedicated promoting broader LNP‐mRNA drugs, aiming advance treatment serious diseases an effective safe manner.

Language: Английский

Citations

5
Ultra-high gene transfection efficiency in suspension cells mediated by highly branched-linear poly(β-amino ester)s DOI
Chenfei Wang,

Tao Bo,

Chen Wu

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 382, P. 113668 - 113668

Published: March 30, 2025

Language: Английский

Citations

0
Administration route-commended concise organ-selective mRNA transfection (ACCOST) by cyclic disulfide-primed short polyethylenimine DOI

Ruonan Ye,

Qiang Ren,

Limin Chang

et al.

Nano Today, Journal Year: 2025, Volume and Issue: 63, P. 102741 - 102741

Published: April 7, 2025

Language: Английский

Citations

0
Aminolysis of Highly Branched Poly(β-amino ester)s for Efficient mRNA Delivery DOI
Haiyang Yong, Zhili Li, Lixin Lin

et al.

Chemistry of Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

Citations

0
Enhancing Gene Transfection Efficiency of Star-Shaped Poly(β-amino ester)s via “Top-down” Hydrolysis DOI

Chenfei Wang,

Feifei Wang,

Yuxing Zheng

et al.

ACS Macro Letters, Journal Year: 2024, Volume and Issue: 13(9), P. 1218 - 1225

Published: Sept. 5, 2024

Gene therapy has emerged as a potent tool for treating wide range of hereditary and acquired disorders. However, the development high-performance nonviral gene delivery vectors remains significant challenge. Here we report new type star-shaped poly(β-amino ester) (SPAE) through "top-down" hydrolysis approach demonstrate its exceptional DNA transfection efficiency safety profiles. Two SPAEs with different monomer combinations are first synthesized using an "arm first" strategy then hydrolyzed sequentially to produce h-SPAEs varied chemical compositions molecular weights. Results that significantly influences physiological characteristics resulting h-SPAE/DNA polyplexes. Dependent on composition, low moderate degrees exhibit superior cell viability across various types. Notably, leading candidate, h-SPAE-1-5h, achieves up 88.8% efficiency, which was 154-257% higher compared SPAE-1. This study not only establishes easy-to-operate reshaping topological structure composition SPAEs, but also identifies promising candidates effective transfection. can be applied other cationic polymers enhance their performance.

Language: Английский

Citations

3
Paracyclophane-based ionizable lipids for efficient mRNA delivery in vivo DOI

Shiqi Wu,

Kexin Su, Xinxin Yan

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 395 - 401

Published: Oct. 20, 2024

Language: Английский

Citations

3
Interaction design in mRNA delivery systems DOI
Mengyao Yu, Lixin Lin, Dezhong Zhou

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 377, P. 413 - 426

Published: Nov. 26, 2024

Language: Английский

Citations

2
Synthetic nanomaterials for spleen-specific mRNA delivery DOI

Shihong Nie,

Beiqi Yang,

Ruiying Ma

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122859 - 122859

Published: Sept. 28, 2024

Language: Английский

Citations

1