Co-encapsulated resveratrol and paclitaxel in liposomes coating with RGDfC peptide for drug resistance reversal in renal cell carcinoma.

BACKGROUND

Drug resistance critically impedes renal cell carcinoma therapy. A dual-targeted liposomal system that codelivered resveratrol (RES) and paclitaxel (PTX) with αvβ3 integrin-targeting was developed to overcome multidrug resistance (MDR).

METHODS

RGDfC peptide-functionalized liposomes (PTX/RES-RGDfC-Lip) were synthesized via film hydration-ultrasound methods. The particle size, zeta potential, drug encapsulation efficiency, and release kinetics were evaluated. P-glycoprotein (P-gp) modulation, cellular uptake, and chemosensitization in PTX-resistant A498 cells (PTX-res-A498) and in vivo antitumor efficacy were studied in xenograft models.

RESULTS

The RGDfC ligand enables selective tumor delivery by binding to αvβ3 integrins that are overexpressed in the renal carcinoma vasculature, whereas RES enhances PTX efficacy by modulating P-gp-mediated drug efflux. Liposomes were synthesized via film hydration-ultrasound methods and systematically characterized for size (109.8 ± 4.2 nm), zeta potential (-8.91 ± 0.75 mV), dual-drug encapsulation efficiency (RES: 90.56 ± 4.30%; PTX: 90.23 ± 4.66%), and sustained release kinetics. In vitro studies demonstrated 3.19-fold greater cellular uptake in resistant renal carcinoma cells (PTX-res-A498 cells) than in nontargeted formulations. In vivo, PTX/RES-RGDfC-Lip resulted in 70.2% tumor reduction in xenograft models. Mechanistic studies confirmed the RES-mediated downregulation of P-gp expression and the restoration of chemosensitivity.

CONCLUSION

This dual-targeted codelivery system represents a promising strategy for overcoming MDR in advanced renal carcinoma.