A Multifunctional Cascade Bioreactor Based on Hollow-Structured Cu2MoS4 for Synergetic Cancer Chemo-Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy

被引：444

作者：

Chang, Mengyu ^{[1
,2
]}

Wang, Man ^{[3
]}

Wang, Meifang ^{[1
,2
]}

Shu, Mengmeng ^{[1
]}

Ding, Binbin ^{[1
,2
]}

Li, Chunxia ^{[3
]}

Pang, Maolin ^{[1
]}

Cui, Shuzhong ^{[4
]}

Hou, Zhiyao ^{[4
,5
]}

Lin, Jun ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China

[2] Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China

[3] Zhejiang Normal Univ, Key Lab, Minist Educ Adv Catalysis Mat, Jinhua 321004, Zhejiang, Peoples R China

[4] Guangzhou Med Univ, Dept Abdominal Surg, Affiliated Canc Hosp & Inst, 78 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China

[5] Guangzhou Med Univ, Sch Basic Med Sci, Guangzhou Municipal & Guangdong Prov Key Labrotor, Guangzhou 511436, Guangdong, Peoples R China

来源：

ADVANCED MATERIALS | 2019年 / 31卷 / 51期

基金：

中国国家自然科学基金;

关键词：

cancer metastasis inhibition; cascade reaction; immune system activation; PEGylated CMS@GOx; synergistic therapy; PHOTODYNAMIC THERAPY; PHOTOTHERMAL THERAPY; NANOPARTICLES; IMMUNOTHERAPY;

D O I：

10.1002/adma.201905271

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+, Mo4+/6+) exhibit Fenton-like, glutathione (GSH) peroxidase-like and catalase-like activity. Once internalized into the tumor, CMS could generate center dot OH for CDT via Fenton-like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase-like CMS could react with endogenous H2O2 to generate O-2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2O2. The regenerated H2O2 can devote to Fenton-like reaction for realizing GOx-catalysis-enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor-killing ability by phototherapy due to its excellent photothermal conversion efficiency (eta = 63.3%) and cytotoxic superoxide anion (center dot O-2(-)) generation performance. More importantly, the PEGylated CMS@GOx-based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.

引用

页数：10