PMID- 34930285 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20220311 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 19 IP - 1 DP - 2021 Dec 20 TI - A cascade targeting strategy based on modified bacterial vesicles for enhancing cancer immunotherapy. PG - 434 LID - 10.1186/s12951-021-01193-9 [doi] LID - 434 AB - BACKGROUND: As an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application. RESULTS: Herein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuated Salmonella outer membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody. CONCLUSIONS: Interesting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing "vaccine effects", conclusively highlighting its potential in preventing tumor recurrence and improving prognosis. CI - (c) 2021. The Author(s). FAU - Zhai, Yuewen AU - Zhai Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. FAU - Ma, Yuying AU - Ma Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. FAU - Pang, Bo AU - Pang B AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China. FAU - Zhang, Jinnan AU - Zhang J AD - Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China. FAU - Li, Ying AU - Li Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. FAU - Rui, Yalan AU - Rui Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. FAU - Xu, Tian AU - Xu T AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. FAU - Zhao, Yu AU - Zhao Y AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China. FAU - Qian, Zhiyu AU - Qian Z AD - Department of Biomedical Engineering, School of Automation, Nanjing University of Aeronautics and Astronautics, 29th JiangJun Street, Nanjing, 211106, Jiangsu, China. FAU - Gu, Yueqing AU - Gu Y AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. gusubmit@163.com. FAU - Li, Siwen AU - Li S AUID- ORCID: 0000-0002-1242-7365 AD - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China. lsw@cpu.edu.cn. LA - eng GR - 81971743/National Natural Science Foundation of China/ GR - 81801835/National Natural Science Foundation of China/ GR - 81827803/National Natural Science Foundation of China/ GR - 8172900016/National Natural Science Foundation of China/ GR - 81727804/National Natural Science Foundation of China/ GR - 91859204/National Natural Science Foundation of China/ GR - BK20200083/Project Supported by the Natural Science Foundation of Jiangsu Province, China/ PT - Journal Article DEP - 20211220 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 0 (Antibodies, Monoclonal) RN - 0 (Liposomes) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (RNA, Small Interfering) RN - EC 3.2.2.6 (ADP-ribosyl Cyclase 1) SB - IM MH - ADP-ribosyl Cyclase 1/antagonists & inhibitors/genetics/metabolism MH - Animals MH - Antibodies, Monoclonal/chemistry/therapeutic use MH - Bacterial Outer Membrane/metabolism MH - Cell Line, Tumor MH - Humans MH - Immunotherapy/*methods MH - Liposomes/chemistry MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred ICR MH - Neoplasms/drug therapy/*therapy MH - Programmed Cell Death 1 Receptor/immunology MH - RNA, Small Interfering/chemistry/therapeutic use MH - Salmonella/metabolism MH - Secretory Vesicles/*chemistry MH - T-Lymphocytes/cytology/immunology/metabolism MH - Transplantation, Heterologous PMC - PMC8686283 COIS- The authors declare no competing financial interest. EDAT- 2021/12/22 06:00 MHDA- 2022/03/12 06:00 PMCR- 2021/12/20 CRDT- 2021/12/21 05:43 PHST- 2021/08/20 00:00 [received] PHST- 2021/12/08 00:00 [accepted] PHST- 2021/12/21 05:43 [entrez] PHST- 2021/12/22 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/12/20 00:00 [pmc-release] AID - 10.1186/s12951-021-01193-9 [pii] AID - 1193 [pii] AID - 10.1186/s12951-021-01193-9 [doi] PST - epublish SO - J Nanobiotechnology. 2021 Dec 20;19(1):434. doi: 10.1186/s12951-021-01193-9.