PMID- 36440740 OWN - NLM STAT- MEDLINE DCOM- 20221222 LR - 20221222 IS - 2047-4849 (Electronic) IS - 2047-4830 (Linking) VI - 11 IP - 1 DP - 2022 Dec 20 TI - Single-component lipid nanoparticles for engineering SOCS1 gene-silenced dendritic cells to boost tumor immunotherapy. PG - 263-277 LID - 10.1039/d2bm01549h [doi] AB - Dendritic cells (DCs) that can prime antitumor responses show great potential in tumor immunotherapy, whereas the unsatisfactory effect which can be ascribed in part to the high expression of inhibitory cytokines, such as the suppressor of cytokine signaling 1 (SOCS1), restricts their application. Thus, silencing these genes in DCs is essential for DC-based therapy. However, safe and effective delivery of siRNA to DCs still faces challenges. Herein, we designed single-component lipid nanoparticles comprising a solely cationic lipid (OA2) for introducing siRNA into mouse DCs in order to inhibit the immunosuppressive gene and boost the effector responses of DC-based therapy. Compared to other multi-component lipid nanoparticles, single-component lipid nanoparticles are theoretically easy-to-control and detective, which is beneficial for future translation. We showed that the application of OA2 lipid nanoparticles significantly downregulated the expression of SOCS1 in DCs over 50%, compared with the commercial lipofectine2000. Besides, the treatment of OA2 lipid nanoparticles had no influence on the antigen capture of DCs. Thus, we fabricated a SOCS1-downregulated DC vaccine pulsed with Ova antigen and demonstrated that the antigen presentation and pro-inflammatory factor secretion ability of DCs were improved due to the SOCS1 downregulation, leading to an ameliorated immunosuppressive tumor microenvironment and finally exhibiting potent tumor prevention and suppression in B16-Ova tumor-bearing mice. Single-component lipid nanoparticles, which provide an available vector platform for siRNA delivery to primary DCs, appear to be a potent tool to engineer DCs and in turn boost DC-based tumor immunotherapy. FAU - Yu, Zexuan AU - Yu Z AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Wu, Mengtong AU - Wu M AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Huang, Yingshuang AU - Huang Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Wang, Yishu AU - Wang Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Chen, Yijun AU - Chen Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Long, Qiulin AU - Long Q AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Lin, Ziming AU - Lin Z AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Xue, Lingjing AU - Xue L AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Ju, Caoyun AU - Ju C AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. FAU - Zhang, Can AU - Zhang C AUID- ORCID: 0000-0003-3529-5438 AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P.R. China. zhangcan@cpu.edu.cn. AD - Chongqing Innovation Institute of China Pharmaceutical University, Chongqing 401135, China. LA - eng PT - Journal Article DEP - 20221220 PL - England TA - Biomater Sci JT - Biomaterials science JID - 101593571 RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 0 (Lipid Nanoparticles) RN - 0 (Suppressor of Cytokine Signaling Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Socs1 protein, mouse) SB - IM MH - Animals MH - Mice MH - Suppressor of Cytokine Signaling 1 Protein/genetics/metabolism MH - *Suppressor of Cytokine Signaling Proteins/genetics/metabolism MH - Immunotherapy MH - *Neoplasms/metabolism MH - Antigen Presentation MH - RNA, Small Interfering/genetics/metabolism MH - Dendritic Cells MH - Mice, Inbred C57BL MH - Tumor Microenvironment EDAT- 2022/11/29 06:00 MHDA- 2022/12/23 06:00 CRDT- 2022/11/28 06:52 PHST- 2022/11/29 06:00 [pubmed] PHST- 2022/12/23 06:00 [medline] PHST- 2022/11/28 06:52 [entrez] AID - 10.1039/d2bm01549h [doi] PST - epublish SO - Biomater Sci. 2022 Dec 20;11(1):263-277. doi: 10.1039/d2bm01549h.