A novel self-assembly albumin nanocarrier for reducing doxorubicin-mediated cardiotoxicity

摘要

Doxorubicin is an antitumor drug commonly used against a wide spectrum of tumors. However, the clinical application of DOX is restricted by its cardiotoxicity. To reduce the cardiotoxicity, we develop an albumin-based nanocarrier via a new molecular switch method for DOX delivery. Spherically shaped DOX-loaded HSA nanoparticles (NPs-DOX) are prepared with a drug-loading capacity and particle size of 4.3% and 120.1 ± 26 nm, respectively. In vivo studies demonstrate that NPs-DOX is able to preferentially accumulate in tumor and show great tumor inhibition on H22 hepatocellular-carcinoma-bearing mice. As for the toxicity, compared with free DOX, the maximum tolerated dose of NPs-DOX is increased from 10 to over 30 mg/kg, indicating the reduced systematic toxicity. More importantly, the cardiotoxicity induced by NPs-DOX is also significantly reduced because both left ventricular ejection fraction and left ventricular fractional shortening are almost not changed and other cardiotoxicity markers such as serum creatine kinase-MB, lactate dehydrogenase, superoxide dismutase, and malonaldehyde are kept constant. The reduced cardiotoxicity of NPs-DOX is also confirmed by nonhistological changes in the heart tissue. Therefore, such albumin-based nanocarrier can be one of the most promising strategies for the delivery of DOX.