Peptide-Conjugated Liposomes for Targeted Mir-34A Delivery to Suppress Breast Cancer and Cancer Stem-Like Population Publisher



Vakhshiteh F¹ ; Khabazian E² ; Atyabi F^{1, 3} ; Ostad SN⁴ ; Madjd Z^{5, 6} ; Dinarvand R^{1, 3}
Source: Journal of Drug Delivery Science and Technology Published:2020

Abstract

MicroRNAs perform critical roles in regulation of cancer cells and cancer stem cells (CSCs). CSCs are key contributors of therapy failure; hence, successful tumor therapy requires elimination of both CSCs and tumor cells. MicroRNA-34a (miR-34a) is a well-defined tumor suppressor microRNA which is hypermethylated in breast cancer. Cyclic RGD (cRGD) is a targeting peptide that selectively target integrin receptor-expressing cells. Herein, cRGD-conjugated Polyethylene glycol-modified (PEGylated) liposomes (cRGD-PEG liposomes) encapsulating miR-34a (cRGD-PEG/miR-34a liposomes) was developed for targeted transport of miR-34a into MDA-MB-231 breast cancer cells. A 1.8-fold higher internalization of cRGD-targeted liposomes effectively increased the accumulation of miR-34a in breast carcinoma cells. Notably, cRGD-targeted miR-34a-loaded liposomes showed significant inhibitory outcome on tumor cell growth, migration, and invasion as well as a significant decrease in the percentage of CD44+/CD24−/low cancer stem-like population. The results suggest that cRGD-targeted liposomes may possibly increase the efficiency of therapeutic MicroRNAs in breast carcinoma cells and CSCs. © 2020 Elsevier B.V.