PMID- 37343780 OWN - NLM STAT- MEDLINE DCOM- 20230925 LR - 20230927 IS - 1549-9642 (Electronic) IS - 1549-9634 (Linking) VI - 53 DP - 2023 Sep TI - Nano-vaccines combining customized in situ anti-PD-L1 depot for enhanced tumor immunotherapy. PG - 102693 LID - S1549-9634(23)00044-8 [pii] LID - 10.1016/j.nano.2023.102693 [doi] AB - Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Chen, Qian AU - Chen Q AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. FAU - Sun, Mengjuan AU - Sun M AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Li, Yanan AU - Li Y AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China. FAU - Huang, Liping AU - Huang L AD - National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. FAU - Zu, Chang AU - Zu C AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Kuang, Xiaoqin AU - Kuang X AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Zhao, Jianing AU - Zhao J AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Hao, Mingyu AU - Hao M AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Ma, Tingting AU - Ma T AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Li, Chunjiayu AU - Li C AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. FAU - Tu, Jiasheng AU - Tu J AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. Electronic address: jiashengtu@cpu.edu.cn. FAU - Sun, Chunmeng AU - Sun C AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. Electronic address: suncmpharm@cpu.edu.cn. FAU - Du, Yunai AU - Du Y AD - NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. Electronic address: duya_cpu@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230619 PL - United States TA - Nanomedicine JT - Nanomedicine : nanotechnology, biology, and medicine JID - 101233142 RN - 0 (Liposomes) RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Lipids) SB - IM MH - Humans MH - *Liposomes/pharmacology MH - Immunotherapy/methods MH - *Melanoma/drug therapy MH - Immune Checkpoint Inhibitors/pharmacology MH - Lipids/pharmacology MH - Tumor Microenvironment OTO - NOTNLM OT - Combination immunotherapy OT - Immune checkpoint blockade OT - Lipid gel OT - Nano-vaccines COIS- Declaration of competing interest There are no conflicts to declare. EDAT- 2023/06/22 01:07 MHDA- 2023/09/25 06:42 CRDT- 2023/06/21 19:16 PHST- 2023/04/23 00:00 [received] PHST- 2023/05/21 00:00 [revised] PHST- 2023/05/29 00:00 [accepted] PHST- 2023/09/25 06:42 [medline] PHST- 2023/06/22 01:07 [pubmed] PHST- 2023/06/21 19:16 [entrez] AID - S1549-9634(23)00044-8 [pii] AID - 10.1016/j.nano.2023.102693 [doi] PST - ppublish SO - Nanomedicine. 2023 Sep;53:102693. doi: 10.1016/j.nano.2023.102693. Epub 2023 Jun 19.