Abstract

Liposomes are among the most extensively applied drug carriers due to their excellent biocompatibility, controllable size and ease of modification. In the present study, we prepared untargeted liposomes (LP) and targeting liposomes modified with Arg-Gly-Asp (RGD-LP), and Doxorubicin Hydrochloride (DOX) or fluorescent probe was loaded. RGD-LP/DOX was identified to be uniformly spherical in size 131.2 ± 2.7 nm. Based on flow cytometry analysis and the confocal laser scanning microscopy, RGD-LP had a higher uptake into HRT-18 colorectal cancer cells than LP. Further, in vivo imaging study further suggested that RGD-LP could significantly increase the liposome accumulation in the tumour tissues of the mice bearing subcutaneous tumours. By investigating the targeting mechanism of RGD-LP, we found that they entered the cell via macropinocytosis. When loaded with DOX, RGD-LP exerted stronger tumour growth inhibitory activity against tumours of colorectal carcinoma compared to LP. Moreover, RGD-LP induced autophagy. Therefore, RGD-LP have the potential to be applied as a targeted colorectal carcinoma therapy.

摘要

脂质体因其优异的生物相容性、可控的大小和易于修饰而成为应用最广泛的药物载体之一。在本研究中，我们制备了非靶向脂质体（LP）和用Arg-Gly-Asp（RGD-LP）修饰的靶向脂质体，并加载了盐酸多柔比星（DOX）或荧光探针。RGD-LP/DOX 被确定为大小为 131.2 ± 2.7 nm 的均匀球形。基于流式细胞术分析和共聚焦激光扫描显微镜，RGD-LP 比 LP 对 HRT-18 结直肠癌细胞的摄取更高。此外，在体内影像学研究进一步表明，RGD-LP 可以显着增加皮下肿瘤小鼠肿瘤组织中脂质体的积累。通过研究RGD-LP的靶向机制，我们发现它们通过巨胞饮作用进入细胞。当装载 DOX 时，与 LP 相比，RGD-LP 对结直肠癌的肿瘤具有更强的肿瘤生长抑制活性。此外，RGD-LP 诱导自噬。因此，RGD-LP有可能被用作靶向结直肠癌治疗。