Targeted Colorectal Cancer Therapy Using Cabozantinib‐Loaded PLGA Nanoparticles: Formulation, Cytotoxicity, and Molecular Docking Analysis

ABSTRACT

The present study represents improved Cabozantinib delivery via Cabozantinib‐loaded poly(lactic‐co‐glycolic acid) nanoparticles, prepared by solvent evaporation. Nanoparticles had a size of 249.5 ± 12.9 nm, a polydispersity index of 0.18, a zeta potential of +2.61 mV, and an encapsulation efficiency of 19% w/w, reflecting a homogeneous distribution, enhanced stability, and high encapsulation efficiency. Fourier‐transform infrared (FTIR), x‐ray diffraction (XRD), differential scanning calorimetric (DSC), and Nuclear magnetic resonance (NMR) confirmed successful drug encapsulation and its amorphous state. The formulation illustrated enhanced pH‐sensitive CBZT release at acidic tumor‐like conditions. In vitro HCT116 cell experiments showed that CBZT‐PLGA‐NPs exhibited higher cytotoxicity than the free drug at 2 µg/mL, profoundly reduced cell migration, and enhanced apoptosis. Flow cytometry demonstrated mitochondrial membrane potential impairment and apoptosis initiation. Molecular docking and dynamics represent strong hydrophobic interactions with the BCL‐2 receptor. The HET‐CAM assay demonstrated remarkable anti‐inflammatory effects, with 72.38% ± 1.89% vessel inhibition. This nanoparticle strategy overcomes pharmacokinetic pitfalls of CBZT, which holds promise for targeted colorectal cancer therapeutics, and perhaps beyond.