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

• Published in: Advanced healthcare materials 2024-11, Vol.13 (28), p.e2401743-n/a
• Main Authors: Zheng, Heming, Huang, Lei, An, Guanghui, Guo, Lianshan, Wang, Nannan, Yang, Wenhui, Zhu, Yanqiu
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Artemisinins; Cancer; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; chemo/photodynamic therapy; Dihydroartemisinin; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Free radicals; Glucose oxidase; Glucose Oxidase - chemistry; Glucose Oxidase - metabolism; Glutathione; Hep G2 Cells; Hepatocellular carcinoma; Humans; Hydrogen peroxide; Hydrogen Peroxide - chemistry; Hydroxyl radicals; Indoles - chemistry; Indoles - pharmacology; Iron; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Metal-organic frameworks; Metal-Organic Frameworks - chemistry; Mice; nanocatalytic medicine; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Polymers - chemistry; Porphyrins; Porphyrins - chemistry; Porphyrins - pharmacology; starvation therapy; Therapy; Tumor microenvironment; Tumors
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202401743

The 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. In this study, a novel cascade Fe‐based MOFs nanodrug delivery system MIL‐101(Fe)‐DOX‐DHA@TCPP/GOx@PDA (MDDTG@P) is constructed for triple synergistic hepatocellular carcinoma therapy, in combination with chemodynamic, photodynamic, and starvation therapy, which provides a feasible strategy to promote synergistic modes of cancer therapy.