Polymer-lipid hybrid nanoparticles-based paclitaxel and etoposide combinations for the synergistic anticancer...

In this study, paclitaxel and etoposide-loaded lipid-polymer hybrid nanoparticles (PE-LPN) was successful prepared and evaluated for physicochemical and anticancer effect. Nanosized PE-LPN was obtained with a perfect spherical morphology. PE-LPN exhibited a controlled release of two drugs in a sequential manner. The nanoparticles exhibited a typical endocytosis-mediated cellular uptake in cancer cells. The ratiometric combination of paclitaxel (PTX) and etoposide (ETP) were significantly more cytotoxic than individual drugs. Importantly, superior cytotoxic effect was observed for dual-drug-loaded PE-LPN than cocktail combination at a much lower dose. Similarly, PE-LPN exhibited a significantly higher apoptosis of cancer cells (∼45%) compared to that of any other groups with higher caspase-3 and -8 activity. Importantly, PE-LPN showed a remarkable tumor regression effect and exhibited a 2-fold superior efficacy than free drugs. PE-LPN treated group showed significantly less Ki-67 positive cells (less than 25%) than PTX/ETP and single drug treated groups, suggesting less active cell proliferation and a considerably higher tumor growth inhibition effect. The results collectively showed that combination of drugs could greatly improve the therapeutic property of chemotherapeutic drugs. By combining ETP with PTX (a powerful anticancer drug) in a polymer-lipid hybrid nanoparticle system, therapeutic efficacy could be improved in osteosarcoma treatments.