Dual targeting of breast cancer by chitosan/poly lactic-co-glycolic acid nanodelivery systems: Surface activation with folic acid/aptamers, and co-encapsulated with Sorafenib and quercetin

Abstract

Breast cancer has a high rate of incidence and is one of the leading causes of death worldwide. Therefore, a breakthrough aptamer (Apt)- and folic acid (FA)-targeted chitosan (CS)-poly lactic-co-glycolic acid (PLGA) nanocarrier was developed for co-delivery of sorafenib (So) and quercetin (Qu) to MCF-7 and MDA-MB-231 breast cancer cells. Nanometric size (50 to 110 nm), semi-spherical and spherical shape, rough surface, and near-to-neutral surface charge (3.8 mV) were measured for Apt-PLGA-So-Qu-CS-FA nanocarriers. The So and Qu drugs content was obtained at about 2.85% and 11.63%, respectively. Controlled release (6.3% (So) and 7.2% (Qu) within 2 h) and pH-sensitive drug release was observed for this nanocarrier. MTT assay indicated lower cell viability for MCF-7 cells after treatment with Apt-PLGA-So-Qu-CS-FA nanocarriers (10% cell viability after 24 h treatment with 250 nm; IC₅₀ = 100 nm). Caspase9 and P53 genes expression was increased by 11.8 and 12.8 folds while > 5 folds reduction was observed for Bcl2 expression after treatment with Apt-PLGA-So-Qu-CS-FA. Also, this nanocarrier led to > 90% proptosis and > 10- and 11.5-fold enhancement in SOD and catalase values in MCF-7 cells. Cellular uptake was about 100%, 77%, and 0.5% for MCF-7 cells treated with Apt-PLGA-CS-FA, PLGA-CS-FA, and CS nanocarriers, respectively which shows the impact of dual-targeting. The fabricated dual targeted nanodelivery system would be a potential device against breast cancer.