title: A novel self-assembly albumin nanocarrier for reducing doxorubicin-mediated cardiotoxicity.
abstract: 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.
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P.R. China.
authors: Ahu
authors: A
authors: Yuan
authors: Jinhui
authors: J
authors: Wu
authors: Chenchen
authors: C
authors: Song
authors: Xiaolei
authors: X
authors: Tang
authors: Qian
authors: Q
authors: Qiao
authors: Lili
authors: L
authors: Zhao
authors: Guangming
authors: G
authors: Gong
authors: Yiqiao
authors: Y
authors: Hu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D054715:Cardiotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004452:Echocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004337:Drug Carriers; D012709:Serum Albumin; D004317:Doxorubicin