School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Bioorg Med Chem. 2011 Sep 15;19(18):5520-8. doi: 10.1016/j.bmc.2011.07.041. Epub 2011 Jul 28.
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.
本文报道了一种新型氯卟啉光敏剂 BCPD-18MA 的合成及光生物性质。以乳腺癌 MDA-MB-231 细胞和Lewis 肺癌（LLC）荷瘤 C57BL/6 小鼠为实验模型，研究了载体制备的 BCPD-18MA 脂质体（L-BCPD-18MA）的细胞毒性、细胞摄取、亚细胞定位、体内分布、光动力疗法（PDT）效率、细胞凋亡及组织学分析。结果表明，L-BCPD-18 迅速被 MDA-MB-231 细胞摄取，并部分定位于线粒体。L-BCPD-18 通过 PDT 诱导细胞凋亡。此外，荷瘤 LLC 小鼠体内的 L-BCPD-18MA 分布研究表明，该药物具有快速清除率和良好的皮肤相关肿瘤选择性。最后，BCPD-18 包封于脂质体中导致暗毒性显著降低，体外 PDT 抗肿瘤疗效显著提高。与载体制备的 BPDMA 脂质体（L-BPDMA）相比，L-BCPD-18MA 对 MDA-MB-231 细胞具有低暗毒性和高 PDT 效率。L-BCPD-18MA 在 LLC 荷瘤小鼠中的光动力疗效与 L-BPDMA 相当，表明 L-BCPD-18MA 是一种有潜力的 PDT 抗肿瘤候选药物。
