Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People's Republic of China.
Department of Radiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People's Republic of China.
Int J Nanomedicine. 2024 May 11;19:4163-4180. doi: 10.2147/IJN.S453275. eCollection 2024.
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).
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.
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.
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.
本研究旨在解决肝癌治疗中细胞毒素（CTX）的非特异性毒性问题，并探索将细胞毒素与光敏剂 Ce6 共同负载于碳化 Zn/Co 双金属有机骨架中的应用。目的是实现 CTX 的控制释放和协同光动力治疗，并重点评估对人肝癌细胞系（Hep G2）的抗肿瘤活性。
纯化的眼镜蛇细胞毒素（CTX）和光敏剂 Ce6 被共同负载于碳化 Zn/Co 双金属有机骨架中，得到 RGD-PDA@C-ZIF@（CTX+Ce6）。该制剂采用聚多巴胺和肿瘤穿透肽 RGD 进行表面功能化设计。这种方法旨在促进 CTX 的控制释放并增强光动力治疗的协同作用。RGD-PDA@C-ZIF@（CTX+Ce6）在肿瘤部位的积累是通过 RGD 的主动靶向和增强的通透性和保留（EPR）效应实现的。在酸性肿瘤微环境中，金属有机骨架的多孔结构解体，将 CTX 和 Ce6 释放到肿瘤细胞中。
实验表明，RGD-PDA@C-ZIF@（CTX+Ce6）纳米粒子与近红外激光照射相结合，对人肝癌细胞表现出最佳的抗肿瘤效果。该制剂表现出增强的抗肿瘤活性，而没有明显的全身毒性。
该研究强调了利用金属有机骨架作为一种有效的纳米平台，用于共载细胞毒素和光动力治疗治疗肝癌的潜力。所开发的制剂 RGD-PDA@C-ZIF@（CTX+Ce6）为细胞毒素在肿瘤学中的临床应用提供了一个有前途的途径，为未来的研究和开发提供了坚实的理论基础。
