PMID- 35272223 OWN - NLM STAT- MEDLINE DCOM- 20220405 LR - 20220511 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 283 DP - 2022 Apr TI - Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy. PG - 121462 LID - S0142-9612(22)00101-6 [pii] LID - 10.1016/j.biomaterials.2022.121462 [doi] AB - Although promising, the efficiency of aggregation-induced emission luminogens (AIEgens)-based photodynamic therapy (PDT) is limited by cellular glutathione (GSH). GSH is not a terminal reducing agent but it can be oxidized and subsequently reduced to its original state by reductases to further participate in antioxidant activity. It is therefore imperative to control GSH for effectively inducing oxidation within tumor cells. Recent studies showed that tumor cell metabolism depends mainly on glutamine, which is also the nitrogen and ATP source for GSH synthesis. Therefore, glutamine-based starvation therapy may be effective in enhancing photodynamic therapy. In this work, tumor-derived exosomes were developed for co-delivering AIEgens and proton pump inhibitors (PPI) for tumor combination therapy. Tumor-derived exosomes could specifically deliver drugs to the tumor sites, where PPI inhibited cell glutamine metabolism, suppressed tumor cell GSH and ATP production, and improved the effect of type-I PDT from AIEgens. When used in the treatment of MGC803 gastric cancer subcutaneous model, our system shows a high tumor growth inhibition rate, and even promoting tumor immunogenic death. This is the first work which combine inhibition of glutamine metabolism with PDT, and it has the potential to be applied for future designs of new tumor metabolic therapies and photodynamic systems. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Zhu, Daoming AU - Zhu D AD - Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine Southern Medical University, Guangzhou, Guangdong, 510515, China. FAU - Zhang, Tianfu AU - Zhang T AD - Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology Clear Water Bay, Kowloon, Hong Kong, 999077, China. FAU - Li, Yang AU - Li Y AD - Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; Department of Gastrointestinal Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China; Department of General Surgery, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, China. FAU - Huang, Chunyu AU - Huang C AD - Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education School of Physics and Technology, Wuhan University, Wuhan, 430072, China. FAU - Suo, Meng AU - Suo M AD - Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education School of Physics and Technology, Wuhan University, Wuhan, 430072, China. FAU - Xia, Ligang AU - Xia L AD - Department of Gastrointestinal Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China. FAU - Xu, Youhua AU - Xu Y AD - Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China. Electronic address: yhxu@must.edu.mo. FAU - Li, Guoxin AU - Li G AD - Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: gzliguoxin@163.com. FAU - Tang, Ben Zhong AU - Tang BZ AD - Shenzhen Institute of Molecular Aggregate Science and Engineering, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Shenzhen, Guangdong, 518172, China. Electronic address: tangbenz@cuhk.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220305 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Photosensitizing Agents) RN - 0 (Proton Pump Inhibitors) RN - 0RH81L854J (Glutamine) SB - IM MH - Cell Line, Tumor MH - *Exosomes/metabolism MH - Glutamine/metabolism MH - Humans MH - *Neoplasms/drug therapy/metabolism MH - *Photochemotherapy MH - Photosensitizing Agents/therapeutic use MH - Proton Pump Inhibitors/metabolism/pharmacology/therapeutic use OTO - NOTNLM OT - Aggregation-induced emission luminogens OT - Enhanced type-I photodynamic therapy OT - Glutamine starvation therapy OT - Proton pump inhibitors OT - Tumor-derived exosomes EDAT- 2022/03/11 06:00 MHDA- 2022/04/06 06:00 CRDT- 2022/03/10 20:16 PHST- 2021/09/29 00:00 [received] PHST- 2022/02/17 00:00 [revised] PHST- 2022/03/05 00:00 [accepted] PHST- 2022/03/11 06:00 [pubmed] PHST- 2022/04/06 06:00 [medline] PHST- 2022/03/10 20:16 [entrez] AID - S0142-9612(22)00101-6 [pii] AID - 10.1016/j.biomaterials.2022.121462 [doi] PST - ppublish SO - Biomaterials. 2022 Apr;283:121462. doi: 10.1016/j.biomaterials.2022.121462. Epub 2022 Mar 5.