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Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy
Zhu, Daoming1; Zhang, Tianfu6; Li, Yang3,4,5,8; Huang, Chunyu7; Suo, Meng7; Xia, Ligang5; Xu, Youhua3,4; Li, Guoxin1; Tang, Ben Zhong2
2022-04-01
Source PublicationBiomaterials
ISSN0142-9612
Volume283
Abstract

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.

KeywordAggregation-induced Emission Luminogens Enhanced Type-i Photodynamic Therapy Glutamine Starvation Therapy Proton Pump Inhibitors Tumor-derived Exosomes
DOI10.1016/j.biomaterials.2022.121462
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000786604900002
PublisherELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
Scopus ID2-s2.0-85126791427
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorXu, Youhua; Li, Guoxin; Tang, Ben Zhong
Affiliation1.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
2.Shenzhen Institute of Molecular Aggregate Science and Engineering, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Guangdong, 518172, China
3.Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, Macao
4.School of Pharmacy, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, Macao
5.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, Guangdong, 518020, China
6.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, Hong Kong
7.Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education School of Physics and Technology, Wuhan University, Wuhan, 430072, China
8.Department of General Surgery, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Zhu, Daoming,Zhang, Tianfu,Li, Yang,et al. Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy[J]. Biomaterials, 2022, 283.
APA Zhu, Daoming., Zhang, Tianfu., Li, Yang., Huang, Chunyu., Suo, Meng., Xia, Ligang., Xu, Youhua., Li, Guoxin., & Tang, Ben Zhong (2022). Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy. Biomaterials, 283.
MLA Zhu, Daoming,et al."Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy".Biomaterials 283(2022).
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