Department of Chemical Engineering, National Institute of Technology, Nara college, Yata 22, Yamato-koriyama, Nara 639-1080, Japan.
Photochem Photobiol Sci. 2019 Jun 12;18(6):1471-1478. doi: 10.1039/c8pp00495a.
We conducted photo-activated delivery of drugs based on the fusion of liposomes with endocytic membranes, thus allowing the direct release of encapsulated drugs inside the cytoplasm. As described in our earlier works, liposomes can be photoresponsive and fusogenic following the incorporation of a malachite green derivative carrying a long alkyl chain (MGL) into the lipid membrane. We prepared MGL liposomes using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine and encapsulated doxorubicin (DOX). Though the shape of MGL liposomes became elliptical after encapsulating DOX, UV irradiation did not enhance DOX leakage from MGL liposomes. We demonstrated the cellular uptake of MGL liposomes into murine cells derived from colon cancer (Colon 26 cells) using flow cytometry, and we found that the uptake was governed by a clathrin-dependent endocytosis pathway. Confocal fluorescence microscopic observations of Colon 26 cells treated with MGL liposomes encapsulating DOX revealed that DOX was localized in endosomes under dark conditions, while DOX was observed in the cytosol and nucleus after UV irradiation. The viability of Colon 26 cells treated with MGL liposomes encapsulating DOX was reduced by UV irradiation, indicating photo-induced enhancement of anti-cancer efficacy.
我们通过将脂质体与内吞膜融合来进行光激活药物递送，从而允许将囊封药物直接释放到细胞质内。如我们之前的工作所述，脂质体可以在长链烷基取代的孔雀石绿衍生物（MGL）掺入脂质膜后具有光响应性和融合性。我们使用 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱制备了 MGL 脂质体，并包封了阿霉素（DOX）。尽管 DOX 包封后 MGL 脂质体的形状变成了椭圆形，但紫外照射并没有增强 DOX 从 MGL 脂质体中的泄漏。我们使用流式细胞术证明了 MGL 脂质体进入源自结肠癌的鼠源细胞（Colon 26 细胞）的细胞摄取，并且我们发现摄取受网格蛋白依赖性内吞作用途径控制。用 DOX 包封的 MGL 脂质体处理的 Colon 26 细胞的共聚焦荧光显微镜观察显示，在黑暗条件下 DOX 位于内体中，而在紫外照射后 DOX 则位于细胞质和核内。用 DOX 包封的 MGL 脂质体处理的 Colon 26 细胞的活力通过紫外照射降低，表明光诱导增强了抗癌功效。
