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, Daoming1,2; Zhang, Tianfu7,8; Li, Yang4,5,6,10; Huang, Chunyu9; Suo, Meng9; Xia, Ligang6; Xu, Youhua4,5; Li, Guoxin1,2; Tang, Ben Zhong3

2022-04-01

10.1016/j.biomaterials.2022.121462

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

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.

Tumor-derived exosomes Aggregation-induced emission luminogens Proton pump inhibitors Glutamine starvation therapy Enhanced type-I photodynamic therapy

SCI ; EI

英语

ESI高被引

其他

Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer[2020B121201004] ; Guangdong Provincial Major Talents Project[2019JC05Y361] ; Science, Technology & Innovation Commission of Shenzhen Municipality[JCYJ20190807144209381] ; Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University[2021J008] ; [FDCT:0093/2018/A3]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000786604900002

ELSEVIER SCI LTD

MATERIALS SCIENCE

Web of Science

1.Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Dept Gen Surg,Key Lab Precis Med Gastrointestinal, Guangzhou 510515, Guangdong, Peoples R China
2.Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Guangdong Prov Key Lab Precis Med Gastrointestina, Guangzhou 510515, Guangdong, Peoples R China
3.Chinese Univ Hong Kong, Shenzhen Inst Mol Aggregate Sci & Engn, Sch Sci & Engn, 2001 Longxiang Blvd, Shenzhen 518172, Guangdong, Peoples R China
4.Macau Univ Sci & Technol, Fac Chinese Med, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China
5.Macau Univ Sci & Technol, Sch Pharm, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China
6.Southern Univ Sci & Technol, Dept Gastrointestinal Surg, Clin Med Coll 2, Jinan Univ,Shenzhen Peoples Hosp,Affiliated Hosp, Shenzhen 518020, Guangdong, Peoples R China
7.Hong Kong Univ Sci & Technol, Dept Chem, Hong Kong Branch Chinese Natl Engn Res Ctr Tissue, Kowloon, Clear Water Bay, Hong Kong 999077, Peoples R China
8.Hong Kong Univ Sci & Technol, Inst Adv Study, Kowloon, Clear Water Bay, Hong Kong 999077, Peoples R China
9.Wuhan Univ, Sch Phys & Technol, Key Lab Artificial Micro & Nanostruct, Minist Educ, Wuhan 430072, Peoples R China
10.Shenzhen Peoples Hosp, Dept Gen Surg, Shenzhen 518020, Guangdong, Peoples R China

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.

Zhu, Daoming.,Zhang, Tianfu.,Li, Yang.,Huang, Chunyu.,Suo, Meng.,...&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.

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).