Physiology of Smart Nanoparticles for Anti-Cancer Drug Delivery

Abstract

Objective: To study the drug loading and release under physiological and acidic conditions and their response to MCF-7 breast cancer cells and HEK293 cells.

Study Design: Experimental study
Place and Duration of Study: This study was conducted at the Almaaqal University College of Dentistry, Basrah, Iraq from 10th May 2025 to 30th September 2025.

Methods: This experimental study made smart nanoparticles that can respond to pH changes. The conjugating folic acid targeting ligands to poly (lactic-co-glycolic acid) or PLGA and DOX or doxorubicin as the anticancer drug were used. The characterization of nanoparticles used DLS, TEM and XPS. The drugs load up and how they release that drug in physiological conditions and acidic conditions. The MCF-7 breast cancer cells and HEK293 normal cells were used for an in vitro cytotoxicity followed by cellular uptake.

Results: The synthesised smart nanoparticles display a uniform spherical morphology with mean diameter of 147.3±8.2 nm and zeta potential of -18.6±2.1 mV. The efficiency of loading of drugs was investigated. 78.4±3.7%
of drug loading efficiency was found. Further, pH-responsive release behavior was investigated which resulted in 23.1% drug release (pH 7.4) and it was 89.7% at 5.0 over 72 hours. Compared with free DOX (IC50 = 11.7±1.2 mM), the smart nanoparticles showed 4.2 times higher cytotoxicity against MCF-7 cells (IC50 = 2.8±0.3 mM). After 24 hours, the drug that we got through SNPs accumulated inside the cell 3.8 times more than the free drug. Selectivity index was 5.6 times higher in cancer cells than in normal cells.

Conclusion: A successfully developed and characterized pH-response smart folate-conjugated doxorubicin nanoparticles for targeted delivery to cancer cells. Smart nanoparticles exhibited the best physicochemical
properties, uniform size distribution, a high drug loading efficiency, and excellent colloidal stability.