Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer

JOURNAL OF CONTROLLED RELEASE

卷:146

Article; Proceedings Paper

Cai, Shuang¹  Thati, Sharadvi¹  Bagby, Taryn R.¹  Diab, Hassam-Mustafa¹  Davies, Neal M.²  Cohen, Mark S.³  Forrest, M. Laird¹ 

[1] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66045 USA

[2] Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA

[3] Univ Kansas, Dept Surg, Med Ctr, Lawrence, KS 66045 USA

关键词: Polymeric drug carrier;    Localized chemotherapy;    Doxorubicin;    Breast cancer;    Localized chemotherapy;   

DOI  :  10.1016/j.jconrel.2010.04.006

来源: Elsevier

【 摘 要 】

Patients with metastatic breast cancer have a five-year survival rate of 27% compared to 98% for localized cancer, and the presence of even a few cancer cells in lymph nodes, known as isolated tumor cells or nanometastases, significantly increases the risk of relapse in the absence of aggressive treatment. Therefore, diagnosis and treatment of lymphatic metastases in early breast cancer plays an important role in patient survival. Here, we demonstrate the first description of a delivery system for localized doxorubicin chemotherapy to the breast tissue. The hyaluronan-doxorubicin nanoconjugate exhibits a sustained release characteristic in vitro and in vivo in the breast tissues of rodents bearing human breast cancer xenografts. In addition, the conjugate reduces dose-limiting cardiac toxicity with minimal toxicity observed in normal tissues. Finally, the conjugate dramatically inhibits breast cancer progression in vivo, leading to an increased survival rate. Thus, localized chemotherapy to the breast lymphatics with a nanocarrier may represent an improved strategy for treatment of early stage breast cancers. (C) 2010 Elsevier B.V. All rights reserved.

【 授权许可】

Free