文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

电荷辅助稳定脂质纳米粒实现吸入型 mRNA 递送至黏膜用于疫苗接种。

Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination.

机构信息

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

Nat Commun. 2024 Nov 2;15(1):9471. doi: 10.1038/s41467-024-53914-x.


DOI:10.1038/s41467-024-53914-x
PMID:39488531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531489/
Abstract

Inhaled delivery of messenger RNA (mRNA) using lipid nanoparticle (LNP) holds immense promise for treating pulmonary diseases or serving as a mucosal vaccine. However, the unsatisfactory delivery efficacy caused by the disintegration and aggregation of LNP during nebulization represents a major obstacle. To address this, we develop a charge-assisted stabilization (CAS) strategy aimed at inducing electrostatic repulsions among LNPs to enhance their colloidal stability. By optimizing the surface charges using a peptide-lipid conjugate, the leading CAS-LNP demonstrates exceptional stability during nebulization, resulting in efficient pulmonary mRNA delivery in mouse, dog, and pig. Inhaled CAS-LNP primarily transfect dendritic cells, triggering robust mucosal and systemic immune responses. We demonstrate the efficacy of inhaled CAS-LNP as a vaccine for SARS-CoV-2 Omicron variant and as a cancer vaccine to inhibit lung metastasis. Our findings illustrate the design principles of nebulized LNPs, paving the way of developing inhaled mRNA vaccines and therapeutics.

摘要

利用脂质纳米颗粒(LNP)吸入传递信使 RNA(mRNA)为治疗肺部疾病或作为黏膜疫苗提供了巨大的潜力。然而,在雾化过程中 LNP 的崩解和聚集导致的递送效果不理想,这是一个主要的障碍。为了解决这个问题,我们开发了一种电荷辅助稳定(CAS)策略,旨在诱导 LNP 之间的静电排斥,以增强其胶体稳定性。通过使用肽脂质缀合物优化表面电荷,领先的 CAS-LNP 在雾化过程中表现出优异的稳定性,从而在小鼠、狗和猪中实现了有效的肺部 mRNA 递送。吸入的 CAS-LNP 主要转染树突状细胞,引发强烈的黏膜和全身免疫反应。我们证明了吸入的 CAS-LNP 作为 SARS-CoV-2 奥密克戎变体疫苗和癌症疫苗抑制肺转移的功效。我们的研究结果说明了雾化 LNP 的设计原则,为开发吸入 mRNA 疫苗和治疗剂铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/dd865663e2bb/41467_2024_53914_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/794f807d7e84/41467_2024_53914_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/337c65b6a0a8/41467_2024_53914_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/bba5febe6b02/41467_2024_53914_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/5e8aa90c9df9/41467_2024_53914_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/426c9ec62a90/41467_2024_53914_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/5106e376f263/41467_2024_53914_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/dd865663e2bb/41467_2024_53914_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/794f807d7e84/41467_2024_53914_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/337c65b6a0a8/41467_2024_53914_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/bba5febe6b02/41467_2024_53914_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/5e8aa90c9df9/41467_2024_53914_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/426c9ec62a90/41467_2024_53914_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/5106e376f263/41467_2024_53914_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5aa/11531489/dd865663e2bb/41467_2024_53914_Fig7_HTML.jpg

相似文献

[1]
Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination.

Nat Commun. 2024-11-2

[2]
ALC-0315 Lipid-Based mRNA LNP Induces Stronger Cellular Immune Responses Postvaccination.

Mol Pharm. 2025-2-3

[3]
SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.

Mol Ther. 2024-5-1

[4]
Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA.

J Am Chem Soc. 2024-11-27

[5]
Laminar fluid ejection device enables high yield and preservation of mRNA and SaRNA LNP formulations.

Sci Rep. 2025-5-27

[6]
Role of PEGylated lipid in lipid nanoparticle formulation for in vitro and in vivo delivery of mRNA vaccines.

J Control Release. 2025-4-10

[7]
Evaluation of mRNA Transfection Reagents for mRNA Delivery and Vaccine Efficacy via Intramuscular Injection in Mice.

ACS Appl Bio Mater. 2025-5-19

[8]
The immunogenic potential of an optimized mRNA lipid nanoparticle formulation carrying sequences from virus and protozoan antigens.

J Nanobiotechnology. 2025-3-18

[9]
Effect of Anti-PEG Antibody on Immune Response of mRNA-Loaded Lipid Nanoparticles.

Mol Pharm. 2024-11-4

[10]
Enhancing protective immunity against SARS-CoV-2 with a self-amplifying RNA lipid nanoparticle vaccine.

J Control Release. 2025-2-10

引用本文的文献

[1]
Construction of Nanotube-Shaped mRNA Vehicles Using Self-Assembling Peptides.

Methods Mol Biol. 2025

[2]
Intranasal mRNA vaccines: Targeting mucosal immunity through optimized delivery.

Mol Ther Nucleic Acids. 2025-8-8

[3]
Harnessing mRNA for heart health: a new era in cardiovascular treatment.

Theranostics. 2025-7-2

[4]
Systematic screening of excipients to stabilize aerosolized lipid nanoparticles for enhanced mRNA delivery.

RSC Pharm. 2025-7-18

[5]
[Advances in inhalable nano-formulations].

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2025-7-3

[6]
Nanomaterial Adjuvants for Veterinary Vaccines: Mechanisms and Applications.

Research (Wash D C). 2025-7-8

[7]
Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging.

Cell Rep Med. 2025-7-15

[8]
Budesonide-incorporated inhalable lipid nanoparticles for antiTSLP nanobody mRNA delivery to treat steroid-resistant asthma.

Nat Commun. 2025-7-1

[9]
Intranasal and Pulmonary Lipid Nanoparticles for Gene Delivery: Turning Challenges into Opportunities.

Int J Nanomedicine. 2025-6-23

[10]
RNA lipid nanoparticles stabilized during nebulization through excipient selection.

Nanoscale Adv. 2025-6-3

本文引用的文献

[1]
Combinatorial development of nebulized mRNA delivery formulations for the lungs.

Nat Nanotechnol. 2024-3

[2]
Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Nat Commun. 2023-11-11

[3]
Adjuvant lipidoid-substituted lipid nanoparticles augment the immunogenicity of SARS-CoV-2 mRNA vaccines.

Nat Nanotechnol. 2023-9

[4]
Intranasal COVID-19 vaccine induces respiratory memory T cells and protects K18-hACE mice against SARS-CoV-2 infection.

NPJ Vaccines. 2023-5-13

[5]
Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing.

Nat Biotechnol. 2023-10

[6]
Biomaterials for intranasal and inhaled vaccine delivery.

Nat Rev Bioeng. 2023-2

[7]
Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung.

Nat Mater. 2023-3

[8]
Tissue resident memory T cells- A new benchmark for the induction of vaccine-induced mucosal immunity.

Front Immunol. 2022

[9]
Engineering Lipid Nanoparticles for Enhanced Intracellular Delivery of mRNA through Inhalation.

ACS Nano. 2022-9-27

[10]
Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8 T cell response.

Proc Natl Acad Sci U S A. 2022-8-23

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索