具有自噬抑制作用的卟啉金属有机框架的制备及其光动力癌症治疗的研究

Preparation of Porphyrin Metal-organic Framework with Autophagy Inhibitory Effect and Its Photodynamic Cancer Treatment

光动力疗法(PDT)具有微创、可控、低毒、可重复治疗等优点,已成为临床医学中不可缺少的治疗手段。但由于肿瘤细胞的自我保护机制,大大降低了PDT疗效。使用PDT治疗方法的同时实施药理自噬抑制策略,切断因光动力治疗下严重氧化损伤下的保护性自噬。通过油浴加热法合成卟啉金属有机框架PCN-224,并在PCN-224上负载自噬抑制剂硫酸羟氯喹(HCQ),通过扫描电子显微镜(SEM)、粒径测试(DLS)、紫外可见光谱测试等方法检测,结果表明成功地合成了该材料,增强了卟啉光敏剂的水溶性,并且光照后对4T1小鼠乳腺癌细胞毒性明显增强,且装载了HCQ后进一步提高了肿瘤杀伤能力。

Photodynamic therapy(PDT)has the advantages of minimally invasive,controllable,low toxicity,and repeatable treatment,and has become an indispensable treatment method in clinical medicine.However,due to the self-protection mechanism of tumor cells,the efficacy of PDT is greatly reduced.This study uses PDT therapy while implementing pharmacological autophagy suppression strategies to cut off protective autophagy under severe oxidative damage due to photodynamic therapy.The porphyrin metal organic framework PCN-224 was synthesized by the oil bath heating method,and the autophagy inhibitor hydroxychloroquine sulfate(HCQ)was loaded on the PCN-224,and the scanning electron microscope(SEM),particle size test(DLS),UV visible spectral testing and other methods showed that the material was successfully synthesized,which enhanced the water solubility of the porphyrin photosensitizer,and significantly enhanced the toxicity to 4T1 mouse breast cancer cells after light,and it further improved the tumor killing ability after being loaded with HCQ.HCQ can be released in tumor cells to deacidify lysosomes and inhibit autophagy,cut off the protective autophagy under severe oxidative damage due to photodynamic therapy,and achieve the effect of killing tumors.