Smart chitosan-PLGA nanocarriers functionalized with surface folic acid ligands against lung cancer cells

Lung cancer is the second most prevalent and first killer cancer worldwide, and conventional approaches do not have enough ability to suppress it. Therefore, a novel targeted chitosan (CS)-poly lactic-co-glycolic acid (PLGA)folic acid (FA) nanocarrier was developed for delivery of sorafenib (Sor) to lung cancer cells. The nanocarrier (CPSF) had a size of 30-40 nm with globular shapes. Surface charge and drug content of CPSF were ascertained at about 1.1 mV and 15 %, respectively. Controlled (4 % within 2 h) and pH-sensitive (18 % within 2 h at pH = 5.0) Sor release were observed for the nanocarrier. The MTT assay demonstrated a cell viability of 13 % after 24 h treatment with 400 nM CPSF in A549 cancer cells while it was 78 % in MSC normal cells. The qRT-PCR revealed >8 folds and 11 folds increase for Caspase9 and P53 genes after 5 h treatment with 100 nM (IC50) CPSF; but a reduction of 5 folds was observed for the Bcl2 gene. Besides, 57 % and 20 % apoptosis were attained in cell cycle arrest and apoptosis assays for CPSF, respectively. CPF indicated about 88 % internalization in cancer cells. These data prove that CPSF is a promising nanodelivery system for lung cancer suppression.

Automated summary

A novel targeted chitosan-based nanocarrier was developed for delivering sorafenib to lung cancer cells, showing controlled and pH-sensitive drug release. MTT assay demonstrated high cytotoxicity in cancer cells but low toxicity in normal cells. qRT-PCR revealed upregulation of Caspase9 and P53 genes and downregulation of Bcl2 gene after treatment with the nanocarrier. Cell cycle arrest and apoptosis assays confirmed the effectiveness of the nanocarrier in inducing apoptosis in cancer cells. Evaluation of internalization showed high uptake of the nanocarrier in cancer cells.