Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation.

【作者】Li, Airong; Liang, Chenglin; Xu, Lihua; Wang, Yiyang; Liu, Wei; Zhang, Kaixiang; Liu, Junjie; Shi, Jinjin

【期刊名】Acta Pharmaceutica Sinica B

【影响因子】2020年: 11.413

【作者单位】School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2021, 5: 1329-1340

【关键词】5-Aminolevulinic acid; Biotransformation interference; Iron ion regulation; DNA repair inhibition; Photodynamic therapy

【摘要】5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

【全文链接】https://www.sciencedirect.com/science/article/pii/S2211383521000903