Doxorubicin and mitomycin C co-loaded polymer-lipid hybrid nanoparticles inhibit growth of sensitive and multidrug resistant human mammary tumor xenografts

Multidrug resistance (MDR) and drug toxicity are two major factors responsible for the failure of cancer chemotherapy. Herein the efficacy and safety of combination therapy using doxorubicin (Dox, D)–mitomycin C (MMC, M) co-loaded stealth polymer-lipid hybrid nanoparticles (DMsPLNs) were evaluated in sensitive and MDR human mammary tumor xenografts. DMsPLN demonstrated enhanced efficacy compared to liposomal Dox (PLD) with up to a 3-fold increase in animal life span, a 10–20% tumor cure rate, undetectable normal tissue toxicity and decreased tumor angiogenesis. These results suggest DMsPLN have potential as an effective treatment of breast cancer.

• Therapeutic efficacy and toxicity of doxorubicin-mitomycin C co-loaded nanoparticles (DMsPLN) were determined. • DMsPLN exhibited enhanced anti-cancer efficacy in both sensitive and multidrug resistant orthotopic breast tumor xenografts. • DMsPLN treatment inhibited tumor angiogenesis. • DMsPLN treatment did not result in any systemic or acute toxicity.