Herceptin-conjugated liposomes co-loaded with doxorubicin and simvastatin in targeted prostate cancer therapy.

ABSTRACT

Prostate cancer (PCa) is a leading cause of cancer-related deaths among men. The anthracycline doxorubicin (DOX) is used for the treatment of this disease, but its considerable side effects and non-selectivity are major drawbacks. Simvastatin (Sim), a lipid-lowering agent, holds great promise as a cancer therapeutic, and thus could be used in combination with DOX. Targeted drug-loaded nano-carriers with antibodies for receptors that are overexpressed on tumor cells are promising strategies for decreasing toxicity to normal tissues and enhancing the efficacy of chemotherapies in cancer treatment. Specifically, human epidermal growth factor 2 is overexpressed and constitutively activated in the PC-3 cell line. Within this context, we designed a co-delivery system coated with Herceptin for PCa, performed physicochemical characterizations, and tested the formulations for cytotoxicity and uptake. The targeted liposomes had a mean particle size of 134 nm, and the drug encapsulation efficiency of both Sim and DOX were greater than 80%. We discovered that the drug combination led to the strong inhibition of PCa both in vitro and in vivo, with inhibitory rates of tumor volumes corresponding to 80.36% and 68.77% of Herceptin-coated liposomes and non-targeted liposomes, respectively. We also found that the anti-tumor mechanisms of the DOX and Sim combination were possibly attributed to synergistic anti-angiogenesis. These results reveal that Herceptin-conjugated liposomes co-loaded with DOX and Sim are a potential novel therapeutic strategy for overcoming PCa.