Nanoparticle-Based Drug Delivery Systems in Targeted Therapy

Abstract

Nanoparticle-based drug delivery systems (NDDS) have emerged as a transformative platform for targeted cancer
therapy, enabling selective accumulation of cytotoxic payloads at tumour sites while reducing systemic toxicity through
passive enhanced permeability and retention (EPR) effect exploitation and active ligand-mediated receptor targeting.
This study designs, synthesises, and characterises four nanoparticle platforms--PLGA polymeric nanoparticles (PNPs),
PEGylated liposomes (PLips), gold nanoparticles (AuNPs), and mesoporous silica nanoparticles (MSNs)--loaded with
doxorubicin (DOX) and functionalised with folate receptor-targeting ligands (folic acid, FA) for selective delivery to folate
receptor-overexpressing cancer cell lines (HeLa, MCF-7, A549). Nanoparticles were comprehensively characterised by
dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, FTIR, and XRD. In vitro drug
release profiling under physiological (pH 7.4) and tumour microenvironment (pH 5.5) conditions demonstrated
pH-responsive release, with MSN-DOX-FA achieving 84.7% cumulative DOX release at pH 5.5 versus 24.3% at pH 7.4
over 72 hours. Cellular uptake quantified by flow cytometry and confocal microscopy showed 3.8-4.6-fold higher uptake
of folate-functionalised versus non-functionalised nanoparticles in FR-overexpressing cells. MTT cytotoxicity assays
demonstrated IC50 values of 0.84-1.47 ug/mL for targeted NDDS versus 8.2-14.7 ug/mL for free DOX in HeLa, MCF-7,
and A549 cells, representing 6-18-fold potency enhancement. In vivo efficacy in HeLa xenograft BALB/c nude mice
showed 74.3% tumour volume reduction with MSN-DOX-FA at day 21 versus 41.8% for free DOX at equivalent dose,
with significantly reduced cardiotoxicity (troponin I: 0.84 vs. 4.21 ng/mL, p < 0.001).