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Published on: February 9, 2019
Smart chitosan-PLGA nanocarriers functionalized with surface folic acid ligands against lung cancer cells
Asghar Narmani1, Saeid Ganji2, Maryam Amirishoar3
1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, 1439957131 Tehran, Iran.
Abstract:
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.
Insights
A novel nanocarrier system, chitosan-poly lactic-co-glycolic acid-folic acid (CPSF), effectively delivers sorafenib to lung cancer cells, showing significant cancer cell death and minimal impact on normal cells.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Lung cancer remains a leading cause of cancer-related death worldwide.
- Conventional treatments for lung cancer often have limitations in efficacy and specificity.
- Targeted drug delivery systems offer a promising strategy to improve lung cancer therapy.
Purpose of the Study:
- To develop and characterize a novel targeted nanocarrier for enhanced delivery of sorafenib to lung cancer cells.
- To evaluate the efficacy of the developed nanocarrier in vitro, assessing its impact on cancer cell viability, apoptosis, and gene expression.
- To investigate the safety profile of the nanocarrier in normal cells.
Main Methods:
- Synthesis and characterization of chitosan-poly lactic-co-glycolic acid-folic acid (CPSF) nanocarriers loaded with sorafenib.
- In vitro drug release studies at different pH conditions.
- Cell viability assays (MTT) on A549 lung cancer cells and MSC normal cells.
- Quantitative real-time PCR (qRT-PCR) to analyze apoptosis-related gene expression (Caspase9, P53, Bcl2).
- Cell cycle arrest and apoptosis assays.
- Cellular internalization studies.
Main Results:
- CPSF nanocarriers exhibited a size of 30-40 nm with a surface charge of 1.1 mV and 15% drug content.
- Controlled and pH-sensitive drug release was observed, with enhanced release at acidic pH (pH 5.0).
- CPSF demonstrated significant cytotoxicity in A549 cancer cells (13% viability at 400 nM) while showing minimal toxicity in MSC normal cells (78% viability).
- Upregulation of Caspase9 and P53, and downregulation of Bcl2 were observed, indicating induction of apoptosis.
- CPSF treatment led to 57% cell cycle arrest and 20% apoptosis, with 88% internalization into cancer cells.
Conclusions:
- The developed CPSF nanocarrier system is a promising platform for targeted delivery of sorafenib in lung cancer therapy.
- CPSF effectively induces apoptosis and suppresses lung cancer cell proliferation with a favorable safety profile.
- Further in vivo studies are warranted to validate the therapeutic potential of CPSF for lung cancer treatment.

