Ultrasound-Activatable Lipid Nanoplatform for Region-Confined Innate Immune Stimulation and mRNA Vaccination Therapy of Cancer
文献类型：期刊论文
| 作者 | Chen, Fangmin9,10,11; Ren, Siyuan8,10,11; Huang, Lujia9,10,11; Wu, Qilong8,10,11; Li, Mengfan7,10,11; Li, Shiqin10,11; Gao, Jing10,11; Lai, Yi10,11; Cai, Zhixiong6; Liu, Xiaolong6 |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
 |
| 出版日期 | 2025-08-25 |
| 页码 | 16 |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/jacs.5c06028 |
| 通讯作者 | Xu, Zhiai(zaxu@chem.ecnu.edu.cn) ; Yu, Haijun(hjyu@simm.ac.cn) |
| 英文摘要 | Adjuvant-integrated lipid nanoparticle (LNP) formulations have been extensively investigated to potentiate mRNA vaccine therapy by promoting innate immune stimulation in antigen-presenting cells (APCs). However, these strategies are challenged by the non-specific and "always on" innate immunostimulatory effects of adjuvants, largely impeding their clinical translation. In this study, we developed a novel LNP component, sono-adjuvant lipid, to endow clinically approved LNP formulations with region-confined adjuvanticity. The engineered ultrasound (US)-activatable LNP (ULNP) precisely boosted innate immune responses in the lymph nodes (LN) through US-triggered activation of the cytosolic DNA-sensing pathways in APCs. Compared to conventional LNP integrating toll-like receptor adjuvant, the combination of ULNP with localized US stimulation (ULNP + US) not only enhanced LN-specific mRNA transfection but also elicited 2.5-fold higher antigen-specific CD8+ T cell responses to inhibit established tumor growth. More importantly, the US-activatable adjuvanting strategy was readily applicable to potentiate tumor neoantigen-encoding circular RNA (circRNA) vaccine therapy. Combining circRNA-loaded ULNP (ci-ULNP) with US stimulation elicited potent antitumor T cell immunity and completely eliminated orthotopic liver tumors in mice. Overall, the sono-adjuvant lipid-integrated ULNP offered a robust platform for spatiotemporally tunable innate immune stimulation and mRNA vaccination therapy of cancer. |
| 资助项目 | National Natural Science Foundation of China[2021YFC2302501] ; Major Project of the Study on Pathogenesis and Epidemic Prevention Technology System by the Ministry of Science and Technology of China[W2412035] ; Major Project of the Study on Pathogenesis and Epidemic Prevention Technology System by the Ministry of Science and Technology of China[U22A20328] ; Major Project of the Study on Pathogenesis and Epidemic Prevention Technology System by the Ministry of Science and Technology of China[82203041] ; Major Project of the Study on Pathogenesis and Epidemic Prevention Technology System by the Ministry of Science and Technology of China[32411530049] ; National Natural Science Foundation of China[XDB1060000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[24430713500] ; Strategic Priority Research Program of the Chinese Academy of Sciences[23ZR1475000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[23490712700] ; Science and Technology Commission of Shanghai Municipality[BJKJ2024046] ; Shanghai Oriental Talents Program[2024M763423] ; China Postdoctoral Science Foundation[BX20250204] ; China National Postdoctoral Program for Innovative Talents[24YF2755800] ; Shanghai Innovation Action Plan Qiming Star Project (Yangfan Special Project)[SKLDR-2023-KF-09] ; Open Funds of the State Key Laboratory of Drug Research ; National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, CAS ; Shanghai Institute of Materia Medica, CAS |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001556319300001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321321]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhiai; Yu, Haijun |
| 作者单位 | 1.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China 2.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China 3.RWTH Aachen Univ Clin, Inst Expt Mol Imaging, Dept Nanomed & Theranost, D-52074 Aachen, Germany 4.Harvard Med Sch, Brigham & Womens Hosp, Dept Anaesthesiol, Boston, MA 02115 USA 5.Harvard Med Sch, Brigham & Womens Hosp, Ctr Nanomed, Boston, MA 02115 USA 6.Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China 7.Jilin Univ, Sch Pharmaceut Sci, Changchun 130021, Jilin, Peoples R China 8.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 9.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Fangmin,Ren, Siyuan,Huang, Lujia,et al. Ultrasound-Activatable Lipid Nanoplatform for Region-Confined Innate Immune Stimulation and mRNA Vaccination Therapy of Cancer[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025:16. |
| APA | Chen, Fangmin.,Ren, Siyuan.,Huang, Lujia.,Wu, Qilong.,Li, Mengfan.,...&Yu, Haijun.(2025).Ultrasound-Activatable Lipid Nanoplatform for Region-Confined Innate Immune Stimulation and mRNA Vaccination Therapy of Cancer.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,16. |
| MLA | Chen, Fangmin,et al."Ultrasound-Activatable Lipid Nanoplatform for Region-Confined Innate Immune Stimulation and mRNA Vaccination Therapy of Cancer".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2025):16. |
入库方式： OAI收割
来源：上海药物研究所
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