PMID- 36933701 OWN - NLM STAT- MEDLINE DCOM- 20230410 LR - 20230521 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 356 DP - 2023 Apr TI - HIF-1 inhibitor-based one-stone-two-birds strategy for enhanced cancer chemodynamic-immunotherapy. PG - 649-662 LID - S0168-3659(23)00193-1 [pii] LID - 10.1016/j.jconrel.2023.03.026 [doi] AB - Based on its ability to induce strong immunogenic cell death (ICD), chemodynamic therapy (CDT) was elaborately designed to combine with immunotherapy for a synergistic anticancer effect. However, hypoxic cancer cells can adaptively regulate hypoxia-inducible factor-1 (HIF-1) pathways, leading to a reactive oxygen species (ROS)-homeostatic and immunosuppressive tumor microenvironment. Consequently, both ROS-dependent CDT efficacy and immunotherapy are largely diminished, further lowering their synergy. Here, a liposomal nanoformulation co-delivering a Fenton catalyst copper oleate and a HIF-1 inhibitor acriflavine (ACF) was reported for breast cancer treatment. Through in vitro and in vivo experiments, copper oleate-initiated CDT was proven to be reinforced by ACF through HIF-1-glutathione pathway inhibition, thus amplifying ICD for better immunotherapeutic outcomes. Meanwhile, ACF as an immunoadjuvant significantly reduced the levels of lactate and adenosine, and downregulated the expression of programmed death ligand-1 (PD-L1), thereby promoting the antitumor immune response in a CDT-independent manner. Hence, the "one stone" ACF was fully taken advantage of to enhance CDT and immunotherapy (two birds), both of which contributed to a better therapeutic outcome. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Zhang, Xiaojuan AU - Zhang X AD - Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiahang Road 118, Jiaxing 314001, People's Republic of China.; School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - He, Chuanchuan AU - He C AD - Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, Zhejiang, China; School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: hechuanchuan@zjxu.edu.cn. FAU - He, Xuelian AU - He X AD - School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Fan, Sijun AU - Fan S AD - School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Ding, Baoyue AU - Ding B AD - Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiahang Road 118, Jiaxing 314001, People's Republic of China. FAU - Lu, Yao AU - Lu Y AD - School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yaolu11@hust.edu.cn. FAU - Xiang, Guangya AU - Xiang G AD - School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; School of Pharmacy, Tongren Polytechnic College, Tongren, Guizhou 554300, China. Electronic address: gyxiang1968@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230321 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - K72T3FS567 (Adenosine) RN - 789U1901C5 (Copper) RN - BBX060AN9V (Hydrogen Peroxide) RN - 0 (Hypoxia-Inducible Factor 1) RN - 2UMI9U37CP (Oleic Acid) RN - 0 (Reactive Oxygen Species) SB - IM MH - Humans MH - Adenosine MH - Cell Line, Tumor MH - *Copper MH - Hydrogen Peroxide MH - *Hypoxia-Inducible Factor 1/antagonists & inhibitors MH - *Immunotherapy MH - *Neoplasms/therapy MH - Oleic Acid MH - Reactive Oxygen Species MH - Tumor Microenvironment OTO - NOTNLM OT - Chemodynamic therapy OT - Hypoxia-inducible factor-1 OT - Immunotherapy OT - Liposome COIS- Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. EDAT- 2023/03/19 06:00 MHDA- 2023/04/05 06:42 CRDT- 2023/03/18 20:29 PHST- 2022/11/01 00:00 [received] PHST- 2023/03/08 00:00 [revised] PHST- 2023/03/14 00:00 [accepted] PHST- 2023/04/05 06:42 [medline] PHST- 2023/03/19 06:00 [pubmed] PHST- 2023/03/18 20:29 [entrez] AID - S0168-3659(23)00193-1 [pii] AID - 10.1016/j.jconrel.2023.03.026 [doi] PST - ppublish SO - J Control Release. 2023 Apr;356:649-662. doi: 10.1016/j.jconrel.2023.03.026. Epub 2023 Mar 21.