Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• Epidermal growth factor receptor (EGFR) overexpression is linked to lung cancer development.
• Targeted therapies offer improved treatment strategies for EGFR-driven cancers.
• Biopolymeric nanoparticles are promising for targeted drug delivery.

Purpose of the Study:

• To evaluate the in vitro effects of docetaxel-loaded, Cetuximab-decorated chitosan-crosslinked γ-poly(glutamic acid) nanoparticles (CET-DTXL-γ-PGA Nps).
• To assess the targeted delivery and anti-cancer activity against EGFR-overexpressing non-small-cell-lung-cancer (NSCLC) cells.
• To compare the efficacy of targeted nanoparticles with non-targeted nanoparticles.

Main Methods:

• Preparation of nanoparticles via ionic gelation and EDC/NHS chemistry for Cetuximab conjugation.
• Confirmation of EGFR specificity through cellular uptake studies in EGFR-positive (A549) and EGFR-negative (NIH3T3) cells.
• In vitro cytotoxicity assessment using MTT, LDH assays, cell-cycle analysis, Annexin V/PI, and JC-1 staining.

Main Results:

• CET-DTXL-γ-PGA Nps demonstrated higher uptake in EGFR-positive A549 cells compared to EGFR-negative cells.
• Targeted nanoparticles exhibited superior antiproliferative activity over non-targeted nanoparticles.
• Treatment induced G2/M cell cycle arrest, reduced mitochondrial membrane potential, and enhanced apoptosis and necrosis in A549 cells.

Conclusions:

• CET-DTXL-γ-PGA Nps show enhanced cellular internalization and therapeutic efficacy by targeting EGFR on NSCLC cells.
• This targeted nanoparticle system represents a potent alternative to conventional chemotherapy, significantly increasing treatment efficiency.
• The developed nanoparticles hold promise for effective treatment of EGFR-overexpressing non-small-cell-lung-cancer.