Fusion peptide functionalized hybrid nanoparticles for synergistic drug delivery to reverse cancer drug resistance

Abstract

A facile self-assembly strategy was developed to decorate polymer/inorganic hybrid nano-sized drug delivery systems with functional peptides. To enhance drug delivery efficacy and overcome tumor drug resistance, a functional fusion peptide containing an RGD sequence for tumor targeting and an R₈ sequence for cell penetration was introduced onto the surface of biotinylated carboxymethyl chitosan/CaCO₃ (BCMC/CaCO₃) hybrid nanoparticles through biotin–avidin interaction to obtain peptide functionalized nanoparticles (PNP). The peptide functionalization results in improved delivery efficiency and effective inhibition for drug resistant tumor cells. Co-delivery of an anti-cancerous drug (doxorubicin hydrochloride, DOX) and a cyclooxygenase-2 inhibitor (celecoxib, CXB) by PNP can further improve the therapeutic efficiency by effectively down-regulating P-gp expression to reduce P-gp mediated drug efflux and increase intracellular drug accumulation.