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用于癌症免疫治疗中mRNA递送的脂质纳米颗粒

Lipid Nanoparticles for mRNA Delivery in Cancer Immunotherapy.

作者信息

Alshehry Yasir, Liu Xiang, Li Wenhua, Wang Qiyan, Cole Janét, Zhu Guizhi

机构信息

Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, United States of America.

Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, 31441, Dammam, Saudi Arabia.

出版信息

AAPS J. 2025 Mar 18;27(3):66. doi: 10.1208/s12248-025-01051-8.


DOI:10.1208/s12248-025-01051-8
PMID:40102316
Abstract

Cancer immunotherapy is poised to be one of the major modalities for cancer treatment. Messenger RNA (mRNA) has emerged as a versatile and promising platform for the development of effective cancer immunotherapy. Delivery systems for mRNA therapeutics are pivotal for their optimal therapeutic efficacy and minimal adverse side effects. Lipid nanoparticles (LNPs) have demonstrated a great success for mRNA delivery. Numerous LNPs have been designed and optimized to enhance mRNA stability, facilitate transfection, and ensure intracellular delivery for subsequent processing. Nevertheless, challenges remain to, for example, improve the efficiency of endosomal escape and passive targeting. This review highlights key advancements in the development of mRNA LNPs for cancer immunotherapy. We delve into the design of LNPs for mRNA delivery, encompassing the chemical structures, characterization, and structure-activity relationships (SAR) of LNP compositions. We discuss the key factors influencing the transfection efficiency, passive targeting, and tropism of mRNA-loaded LNPs. We also review the preclinical and clinical applications of mRNA LNPs in cancer immunotherapy. This review can enhance our understanding in the design and application of LNPs for mRNA delivery in cancer immunotherapy.

摘要

癌症免疫疗法有望成为癌症治疗的主要方式之一。信使核糖核酸(mRNA)已成为开发有效的癌症免疫疗法的一个通用且有前景的平台。mRNA疗法的递送系统对于其最佳治疗效果和最小副作用至关重要。脂质纳米颗粒(LNPs)已在mRNA递送方面取得了巨大成功。人们设计并优化了众多LNPs,以增强mRNA稳定性、促进转染并确保细胞内递送以便后续处理。然而,仍存在一些挑战,例如提高内体逃逸效率和被动靶向性。本综述重点介绍了用于癌症免疫疗法的mRNA-LNPs开发的关键进展。我们深入探讨了用于mRNA递送的LNPs的设计,包括LNP组合物的化学结构、表征以及构效关系(SAR)。我们讨论了影响载有mRNA的LNPs转染效率、被动靶向性和趋向性的关键因素。我们还综述了mRNA-LNPs在癌症免疫疗法中的临床前和临床应用。本综述可增进我们对用于癌症免疫疗法中mRNA递送的LNPs的设计和应用的理解。

相似文献

[1]
Lipid Nanoparticles for mRNA Delivery in Cancer Immunotherapy.

AAPS J. 2025-3-18

[2]
Lipid nanoparticle mediated mRNA delivery in cancer immunotherapy.

Adv Immunol. 2025

[3]
Efficacy versus immunogenicity of LNP-mediated delivery of mRNA and self-amplifying RNA upon intravitreal injection in the mouse eye.

J Control Release. 2025-7-12

[4]
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Eur J Pharm Sci. 2025-6-24

[5]
Biodegradable polymers with tertiary amines enhance mRNA delivery of lipid nanoparticles via improved endosomal escape.

Biomaterials. 2026-1

[6]
Nucleic Acid Nanocapsules as a New Platform to Deliver Therapeutic Nucleic Acids for Gene Regulation.

Acc Chem Res. 2025-7-1

[7]
Engineering Lipid Nanoparticles for mRNA Immunotherapy.

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025

[8]
Lipid Nanoparticles Consisting of Sterol-Conjugated Ionizable Lipids Enable Prolonged and Safe mRNA Delivery.

ACS Appl Mater Interfaces. 2025-6-18

[9]
A perspective on the apparent pKa of ionizable lipids in mRNA-LNPs.

J Control Release. 2025-8-10

[10]
The impact of, and expectations for, lipid nanoparticle technology: From cellular targeting to organelle targeting.

J Control Release. 2024-6

引用本文的文献

[1]
Pia Mater-Penetrable Lipopolymer Nanoparticles for Gliocyte-Targeted IL-10 mRNA Therapy Alleviate Paclitaxel-Induced Peripheral Neuropathy.

Adv Sci (Weinh). 2025-6

本文引用的文献

[1]
Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions.

J Pers Med. 2024-11-4

[2]
Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity.

Sci Adv. 2024-10-11

[3]
Effectiveness and Safety of mRNA Vaccines in the Therapy of Glioblastoma.

J Pers Med. 2024-9-19

[4]
Tailoring lipid nanoparticle dimensions through manufacturing processes.

RSC Pharm. 2024-9-23

[5]
mRNA vaccines: a new era in vaccine development.

Oncol Res. 2024

[6]
Lipid nanoparticle-mediated RNA delivery for immune cell modulation.

Eur J Immunol. 2024-12

[7]
Acid-degradable lipid nanoparticles enhance the delivery of mRNA.

Nat Nanotechnol. 2024-11

[8]
Enhancing spleen-targeted mRNA delivery with branched biodegradable tails in lipid nanoparticles.

J Mater Chem B. 2024-8-22

[9]
Lipid Nanoparticle-mRNA Engineered Dendritic Cell Based Adoptive Cell Therapy Enhances Cancer Immune Response.

Small Methods. 2025-1

[10]
Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation.

Nat Commun. 2024-7-5

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