Nanoparticle-Based Targeted Drug Delivery Systems

Abstract

Conventional chemotherapy distributes cytotoxic agents systemically, with fewer than 5% of administered drug molecules reaching tumour tissue, leading to dose-limiting toxicities in healthy organs -- particularly bone marrow, gastrointestinal epithelium, and cardiac tissue. Nanoparticle-based targeted drug delivery systems (nano-DDS) exploit the enhanced permeability and retention (EPR) effect and active ligand-receptor targeting to concentrate therapeutic payloads within tumour microenvironments while sparing normal tissue. This study designed, synthesised, and evaluated five nanocarrier platforms -- PLGA nanoparticles, PEGylated liposomes, mesoporous silica nanoparticles (MSNs), gold nanorods (AuNRs), and a proposed folate-conjugated polymeric micelle (FA-PM) -- for targeted delivery of doxorubicin (DOX) to folate receptor-overexpressing breast cancer cells (MCF-7, MDA-MB-231). FA-PM achieved the highest tumour-selective cytotoxicity (IC50 0.42 +- 0.08 uM in FR+ MCF-7 vs 8.64 +- 1.22 uM in FR- fibroblasts; selectivity index 20.6), significantly outperforming free DOX (SI 2.4) and non-targeted PLGA NPs (SI 4.8). In vivo evaluation in MCF-7 xenograft-bearing nude mice (n = 60) demonstrated that FA-PM-DOX achieved 78.4 +- 6.2% tumour growth inhibition (TGI) at 5 mg/kg DOX-equivalent, compared to 52.6 +- 8.4% for free DOX (p < 0.001) and 64.8 +- 7.2% for PEGylated liposomal DOX (p = 0.008), with significantly reduced cardiotoxicity (serum CK-MB 124 +- 18 U/L vs 286 +- 42 U/L for free DOX; p < 0.001). These results establish folate-conjugated polymeric micelles as a highly effective targeted nanocarrier platform and provide a systematic framework for benchmarking nano-DDS formulations.