Studies on preparation and photodynamic mechanism of chlorin P6-13,15-N-(cyclohexyl)cycloimide (Chlorin-H) and its antitumor effect for photodynamic therapy in vitro and in vivo.

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer play key roles in the treatment efficacy. In this study, a novel photosensitizer, Chlorin-H [-13,15-N-(cyclohexyl)cycloimide] which displayed a characteristic long wavelength absorption peak at 698nm was synthesized. Following flash photolysis with 355nm laser, Chlorin-H is potent to react with O(2) and then produce (1)O(2). This finding indicates that Chlorin-H takes its effects through type II mechanism in PDT. Generally, Chlorin-H is localized in mitochondria and nucleus of cell. After light irradiation with 698nm laser, it can kill many types of cell, inhibit cell proliferation and colony formation, suppress cancer cell invasiveness and trigger apoptosis via the mitochondrial pathway in A549 cells in vitro. In addition, Chlorin-H-PDT can destroy A549 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following Chlorin-H-PDT. The results showed that it either increased or decrease. Among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. Silencing of TNFSF13 caused by RNA interference decreased the susceptibility of A549 cells to Chlorin-H-PDT. In general, Chlorin-H is an effective antitumor photosensitizer in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new photosensitizers.

Yan YJ ，Zheng MZ ，Chen ZL ，Yu XH ，Yang XX ，Ding ZL ，Xu L ... -  《-》

Synthesis and photobiological study of a novel chlorin photosensitizer BCPD-18MA for photodynamic therapy.

This paper reports synthesis and photobiological properties of a novel chlorin photosensitizer BCPD-18MA. Cytotoxicity, cellular uptake, subcellular location, biodistribution, photodynamic therapy (PDT) efficiency, cell apoptosis as well as histological analysis of the liposomal-delivered BCPD-18MA (L-BCPD-18MA) was studied using mammary adenocarcinoma MDA-MB-231 cells and Lewis lung carcinoma (LLC) implanted in C57BL/6 mice as experimental models. The results showed that L-BCPD-18 was incorporated rapidly into MDA-MB-231 cells and localized partially in mitochondria. L-BCPD-18 induced cell apoptosis by PDT. In addition, biodistribution of L-BCPD-18MA in LLC-bearing mice demonstrated a fast clearance rate of the drug and good skin-related tumor selectivity. Finally, entrapment of BCPD-18 into liposomes resulted in a dramatic impairment of dark toxicity and a notable improvement of PDT antitumor efficacy in vitro. Compared with liposomal-delivered BPDMA (L-BPDMA), L-BCPD-18MA exhibited low dark toxicity and high PDT efficiency on MDA-MB-231 cells. The photodynamic efficacy of L-BCPD-18MA on LLC-bearing mice is comparable to that of L-BPDMA, implying that L-BCPD-18MA is a potential antitumor candidate for PDT.

Zhang J ，Deng L ，Yao J ，Gu P ，Yang F ，Wang X ，Liu W ，Zhang Y ，Ke X ，Jing X ，Chen J ... -  《-》

A next-generation bifunctional photosensitizer with improved water-solubility for photodynamic therapy and diagnosis.

Nishie H ，Kataoka H ，Yano S ，Kikuchi JI ，Hayashi N ，Narumi A ，Nomoto A ，Kubota E ，Joh T ... -  《Oncotarget》

Antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy can be enhanced by the use of a low dose of photofrin in human tumor xenografts.

Peng Q ，Warloe T ，Moan J ，Godal A ，Apricena F ，Giercksky KE ，Nesland JM ... -  《CANCER RESEARCH》

Tissue distribution and in vivo photosensitizing activity of 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester.

Karmakova T ，Feofanov A ，Pankratov A ，Kazachkina N ，Nazarova A ，Yakubovskaya R ，Lebedeva V ，Ruziyev R ，Mironov A ，Maurizot JC ，Vigny P ... -  《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY》