Metallic Copper-Based Dual-Enzyme Biomimetic Nanoplatform for Mild Photothermal Enhancement of Anticancer Catalytic Activity

作者全名：Chen, Ziqun; Li, Ying; Xiang, Qi; Wu, Yunfang; Ran, Haitao; Cao, Yang

作者地址：[Chen, Ziqun; Li, Ying; Xiang, Qi; Wu, Yunfang; Ran, Haitao; Cao, Yang] Chongqing Med Univ, Affiliated Hosp 2,Inst Ultrasound Imaging,Ultrasou, State Key Lab Ultrasound Med & Engn, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China

通信作者：Cao, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2,Inst Ultrasound Imaging,Ultrasou, State Key Lab Ultrasound Med & Engn, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.

来源：BIOMATERIALS RESEARCH

ESI学科分类：　

WOS号：WOS:001244967500001

JCR分区：Q1

影响因子：8.1

年份：2024

卷号：28

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Background: Chemodynamic therapy (CDT) is recognized as a promising cancer treatment. Recently, copper sulfide nanostructures have been extensively employed as Fenton-like reagents that catalyze the formation of acutely toxic hydroxyl radicals (<middle dot>OH) from hydrogen peroxide (H2O2). However, CDT therapeutic potency is restricted by the tumor microenvironment (TME), such as insufficient amounts of hydrogen peroxide, excessive glutathione levels, etc. To address these disadvantages, glucose oxidase (GOx) or catalase (CAT) can be utilized to enhance CDT, while low therapeutic efficacy still inhibits their future applications. Our previous study revealed that mild photothermal effect could boost the CDT catalytic effectiveness as well as GOx enzyme activity over a range. Results: We engineered and constructed a hollow CuS nanoplatform loaded with GOx and CAT, coating with macrophage membranes (M@GOx-CAT@ CuS NPs). The nanoplatforms allowed enhancement of the reactive oxygen species creation rate and GOx catalytic activeness of CDT through mild phototherapy directed by photoacoustic imaging. After actively targeting vascular cell adhesion molecule-1 (VCAM-1) in cancer cells mediated by macrophage membrane coating, M@GOx-CAT@CuS NPs released GOx and CAT under near-infrared irradiation. GOx catalyzed the formation of H2O2 and gluconic acid with glucose, creating a better catalytic environment for CDT. Meanwhile, CAT-catalyzed H2O2 decomposition to generate sufficient oxygen, appropriately alleviating the oxygen shortage in the TME. In addition, starvation effects decreased adenosine triphosphate levels and further underregulated heat shock protein expression to reduce the heat resistance of tumor cells, resulting in a better mild phototherapy outcome. Both in vitro and in vivo experiments demonstrated that the newly developed M@GOx-CAT@CuS nanoplatform has remarkable synergistic anticancer therapeutic effects. Conclusion: The cascade reaction-enhanced biomimetic nanoplatform opens up a new avenue for precision tumor diagnostic and therapeutic research.

基金机构：Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0120]; Senior Medical Talents Program of Chongqing for Young and Middle-aged, and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University

基金资助正文：Funding: This work was funded by the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0120) , Senior Medical Talents Program of Chongqing for Young and Middle-aged, and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.