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.

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.