title: Synthesis and photobiological study of a novel chlorin photosensitizer BCPD-18MA for photodynamic therapy.
abstract: 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.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Peng
authors.initials: P
authors.lastname: Gu
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Xiuxin
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xingfa
authors.initials: X
authors.lastname: Ke
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Jing
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; C569132:BCPD-18MA; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin