Surface-Engineered Extracellular Vesicles with CDH17 Nanobodies to Efficiently Deliver Imaging Probes and Chemo-Photothermal Drugs for Gastric Cancer Theragnostic

被引：15

作者：

Xia, Peng ^{[1
,2
,3
]}

Yuan, Haitao ^{[1
,2
]}

Tian, Ming ^{[3
]}

Zhong, Tianyu ^{[4
]}

Hou, Rui ^{[5
,6
]}

Xu, Xiaolong ^{[1
,2
]}

Ma, Jingbo ^{[1
,2
]}

Wang, Huifang ^{[1
,2
]}

Li, Zhifen ^{[7
]}

Huang, Defa ^{[4
]}

Qu, Chengming ^{[3
]}

Dai, Lingyun ^{[1
,2
]}

Xu, Chengchao ^{[1
,2
]}

Yang, Chuanbin ^{[1
,2
]}

Jiang, Haibo ^{[8
]}

He, Yuanqiao ^{[9
]}

Rueckert, Felix

Li, Zhijie ^{[1
,2
]}

Yuan, Yufeng ^{[3
]}

Wang, Jigang ^{[1
,2
,10
,11
,12
]}

机构：

[1] Southern Univ Sci & Technol, Shenzhen Inst Resp Dis, Shenzhen 518020, Guangdong, Peoples R China

[2] Southern Univ Sci & Technol, Jinan Univ, Shenzhen Clin Res Ctr Respirol,Shenzhen Peoples, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China

[3] Zhongnan Hosp Wuhan Univ, Dept Hepatobiliary & Pancreat Surg, Wuhan 430062, Hubei, Peoples R China

[4] Gannan Med Univ, Lab Med, Ganzhou 341000, Jiangxi, Peoples R China

[5] Univ Western Australia, Harry Perkins Inst Med Res, QEII Med Ctr, Nedlands, WA 6009, Australia

[6] Univ Western Australia, Ctr Med Res, Nedlands, WA 6009, Australia

[7] Shanxi Datong Univ, Sch Chem & Chem Engn, Xing Yun St, Datong 037009, Shanxi, Peoples R China

[8] Univ Hong Kong, Dept Chem, Hong Kong 999077, Peoples R China

[9] Nanchang Univ, Sch Med, Nanchang 330031, Jiangxi, Peoples R China

[10] Diakonissen Hosp, Dept Visceral Surg, D-67346 Speyer, Germany

[11] China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China

[12] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

来源：

ADVANCED FUNCTIONAL MATERIALS | 2023年 / 33卷 / 07期

基金：

中国国家自然科学基金;

关键词：

chemotherapy; extracellular vesicles; nanobodies; photothermal therapy; targeted delivery; BREAST-CANCER; EXOSOMES; THERAPY; RRX-001; NANOPARTICLE; METASTASIS; RELEASE; AGENT; CELLS;

D O I：

10.1002/adfm.202209393

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Extracellular vesicles (EVs) are widely used as natural nanoparticles to deliver various cargos for disease diagnosis and therapy. However, unmodified EVs cannot efficiently transport the cargos to desired sites due to non-specific uptake. Here, a delivery system is designed to display nanobodies against cadherin 17 (CDH17) on the surface of EVs isolated from HEK-293 cells and loaded with dye Indocyanine green (ICG) and/or anti-cancer drug dinitroazetidine derivative RRx-001, a blocker for CD47/ signal regulatory protein alpha (SIRP alpha) axis. CDH17 is a promising target for gastric cancer (GC) therapy. In this study, ICG loaded in the EVs engineered with CDH17 nanobodies can realize rapid tumor imaging in a CDH17-positive GC model and can produce significant anti-tumor photothermal therapeutic (PTT) effect after irradiation. Meanwhile, PTT effect can induce immunogenic cell death and macrophage polarization from M2 to M1 phenotype. The engineered EVs loaded with RRx-001 can significantly repress GC tumor growth. Finally, dual loading of ICG/RRx-001 in engineered EVs show maximal anti-tumor efficacy in both cancer cell and patient-derived GC models after only single injection. Collectively, CDH17 nanobody-functionalized EVs loaded with ICG and/or RRx-001 hold great promise to image and treat GC by combining fluorescent dye-induced PTT with chemotherapy.

引用

页数：20