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

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.