A Nanoreactor Based on Metal–Organic Frameworks With Triple Synergistic Therapy for Hepatocellular Carcinoma

Author:

Zheng Heming1,Huang Lei2,An Guanghui1,Guo Lianshan3,Wang Nannan1ORCID,Yang Wenhui4,Zhu Yanqiu15

Affiliation:

1. State Key Laboratory of Featured Metal Materials and Life‐cycle Safety for Composite Structures MOE Key Laboratory of New Processing Technology for Nonferrous Metals and Materials and School of Resources Environment and Materials Guangxi University Nanning 530004 China

2. School of Stomatology Minzhu Clinic of Stomatology Hospital Affiliated to Guangxi Medical University Guangxi 530007 China

3. Department of Nephrology The Second Affiliated Hospital of Guangxi Medical University Nanning Guangxi 530007 China

4. Department of Medical Laboratory The People's Hospital of Guangxi Zhuang Autonomous Region Nanning Guangxi 530021 China

5. College of Engineering Mathematics and Physical Sciences University of Exeter Exeter EX4 4QF UK

Abstract

AbstractThe transformation of monotherapy into multimodal combined targeted therapy to fully exploit synergistic efficacy is of increasing interest in tumor treatment. In this work, a novel nanodrug‐carrying platform based on iron‐based MOFs, which is loaded with doxorubicin hydrochloride (DOX), dihydroartemisinin (DHA), and glucose oxidase (GOx), and concurrently covalently linked to the photosensitizer 5,10,15,20‐tetrakis(4‐carboxyphenyl)porphyrin (TCPP) in polydopamine (PDA)‐encapsulated MIL‐101(Fe) (denoted as MIL‐101(Fe)‐DOX‐DHA@TCPP/GOx@PDA, MDDTG@P), is successfully developed. Upon entering the tumor microenvironment, MDDTG@P catalyzes the hydrogen peroxide (H2O2) into hydroxyl radicals (·OH) and depletes glutathione (GSH); thus, exerting the role of chemodynamic therapy (CDT). The reduced Fe2+ can also activate DHA, further expanding CDT and promoting tumor cell apoptosis. The introduced GOx will rapidly consume glucose and oxygen (O2) in the tumor; while, replenishing H2O2 for Fenton reaction, starving the cancer cells; and thus, realizing starvation and chemodynamic therapy. In addition, the covalent linkage of TCPP endows MDDTG@P with good photodynamic therapeutic (PDT) properties. Therefore, this study develops a nanocarrier platform for triple synergistic chemodynamic/photodynamic/starvation therapy, which has promising applications in the efficient treatment of tumors.

Publisher

Wiley

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