Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer

Abstract

Jingmei Huang,1,* Lianshan Guo,1,* Xiaoxiao Huang,1 Xiaoping Yu,2 Liqiao Lin,1 Xinlin Jiang,3 Zhihao Bai,4 Zhengzhao Li1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 3Department of General Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengzhao Li, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China, Email [email protected] Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China, Email [email protected]: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2).Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD’s active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells.Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity.Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.Keywords: metal-organic frameworks, cytotoxins, photodynamic therapy, liver cancer

Keywords

• metal-organic frameworks
• cytotoxins
• photodynamic therapy
• liver cancer