Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers

Abstract

Context: Breast cancer is the most common cancer in female population. Breast cancer chemotherapy using doxorubicin (DOX) is well illustrated. However, a significant obstacle for successful chemotherapy with DOX is multidrug resistant (MDR) in breast cancer cells. Targeted nanocarriers have emerged as frontier research for the improvement of cancer chemotherapy.Objective: Bombesin (Bn)-modified, DOX-loaded solid lipid nanoparticles (Bn-DOX/SLNs) were constructed. Doxorubicin-resistant MCF-7/MDR human breast cancer cells and the cancer animal models were applied for the evaluation of the in vitro and in vivo anti-tumor effect of Bn-DOX/SLNs.Methods: Bn-conjugated lipids were synthesized. DOX was then loaded into Bn-modified SLNs. The physicochemical properties of the Bn-DOX/SLNs were investigated by particle size and zeta potential measurement, drug loading and drug-entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against MCF-7/MDR cells was investigated, and in vivo anti-tumor of SLNs was evaluated in human breast cancer mice models.Results: Bn-DOX/SLNs showed an excellent in vitro cytotoxicity and in vivo anti-tumor effect both in MCF-7/MDR breast cancer cells and breast cancer animal model.Conclusion: The results demonstrated that Bn-DOX/SLNs reversed the resistance of doxorubicin, suggesting that chemotherapy using this kind of targeted nanocarriers may benefit human breast MDR cancer therapy.