Delivery of RGD-modified liposome as a targeted colorectal carcinoma therapy and its autophagy mechanism

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.

Keywords:

• RGD peptide
• liposomes
• colorectal drug targeting
• targeting mechanism
• autophagy

Disclosure statement

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81703426); Natural Science Foundation of Heilongjiang Province (LH2019H010); Natural Science Foundation of Heilongjiang Province (H2018018); China Postdoctoral Science Foundation (2019M651312); Heilongjiang Postdoctoral Fund (LBH-Z18106); Health Commission of Heilongjiang Province (2017-170); the Mentor Found (XQJJ2016003) of Daqing campus, Harbin Medical University; and Innovation and Entrepreneurship Programme for College Students in Heilongjiang Province (201910226137); Key research and development and promotion projects of Henan Province (192102310154); Innovation and entrepreneurship training program of Zhengzhou University (202010459148).