Background: The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.
Methods: A functional hybrid peptide (MTS-R₈H₃) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R₈H₃ lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.
Results: DOX/CEL-MTS-R₈H₃ lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R₈H₃ peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.
Conclusion: The study suggested that the DOX/CEL-MTS-R₈H₃ lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.
Keywords: doxorubicin hydrochloride, celecoxib, co-delivery, targeting liposomes, multidrug resistance