Gong Bin, Zhang Qiuyun, Qu Yijie, Zheng Xiaohua, Wang Weiqi
The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang 212300, China.
School of Pharmacy, Nantong University, Nantong 226001, China.
Pharmaceutics. 2025 Jul 4;17(7):883. doi: 10.3390/pharmaceutics17070883.
The phototherapeutic applications of porphyrin-based nanoscale metal-organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the problems of low energy conversion efficiency, requiring a relatively high radiation dose, and the potential to cause damage to normal tissues. Researchers have found that by using some metals with high atomic numbers (high Z) as X-ray scintillators and coordinating them with porphyrin photosensitizers to form MOF materials, the excellent antitumor effect of radiotherapy (RT) and RDT can be achieved under low-dose X-ray irradiation, which can not only effectively avoid the penetration limitations of light excitation methods but also eliminate the defect issues associated with directly using X-rays to excite photosensitizers. This review summarizes the relevant research work in recent years, in which researchers have used metal ions with high Z, such as Hf, Th, Ta, and Bi, in coordination with carboxyl porphyrins to form MOF materials for combined RT and RDT toward various cancer cells. This review compares the therapeutic effects and advantages of using different high-Z metals and introduces the application of the heavy atom effect. Furthermore, it explores the introduction of a chemodynamic therapy (CDT) mechanism through iron coordination at the porphyrin center, along with optimization strategies such as oxygen delivery using hemoglobin to enhance the efficacy of these MOFs as radiosensitizers. This review also summarizes the potential of these materials in preclinical applications and highlights the current challenges they face. It is expected that the summary and prospects outlined in this review can further promote preclinical biomedical research into and the development of porphyrin-based nMOFs.
基于卟啉的纳米级金属有机框架（nMOF）的光治疗应用受到传统激发光源对生物组织穿透性差的限制。放射动力疗法（RDT）直接利用X射线激发光敏剂，可克服组织穿透问题。然而，RDT面临能量转换效率低、需要相对高的辐射剂量以及可能对正常组织造成损伤等问题。研究人员发现，通过使用一些高原子序数（高Z）的金属作为X射线闪烁体，并将它们与卟啉光敏剂配位形成MOF材料，可在低剂量X射线照射下实现放射疗法（RT）和RDT的优异抗肿瘤效果，这不仅能有效避免光激发方法的穿透限制，还能消除直接使用X射线激发光敏剂相关的缺陷问题。本综述总结了近年来的相关研究工作，其中研究人员使用高Z金属离子，如铪、钍、钽和铋，与羧基卟啉配位形成MOF材料，用于对各种癌细胞进行联合RT和RDT。本综述比较了使用不同高Z金属的治疗效果和优势，并介绍了重原子效应的应用。此外，还探讨了通过在卟啉中心进行铁配位引入化学动力疗法（CDT）机制，以及诸如使用血红蛋白进行氧气输送等优化策略，以提高这些MOF作为放射增敏剂的疗效。本综述还总结了这些材料在临床前应用中的潜力，并突出了它们目前面临的挑战。预计本综述中的总结和展望能够进一步推动基于卟啉的nMOF的临床前生物医学研究和开发。
