A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery.
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| Abstract |
Doxorubicin (DOX) is one of the most effective anti-cancer drugs, but its therapeutic efficacy is greatly hampered by its non-specific delivery to the target tissue and the resultant cumulative cardiotoxicity and nephrotoxicity. In order to overcome this limitation, we prepared a folate-bovine serum albumin (BSA)-cis-aconitic anhydride-doxorubicin prodrug, denoted by FA-BSA-CAD. A tumor-targeting agent, folic acid, was linked to BSA to increase the selective targeting ability of the conjugate. BSA provided a large number of reactive sites for multivalent coupling of bioactive molecules and improved the water-solubility of the prodrug. DOX is attached to the BSA via a pH-sensitive linker, cis-aconitic anhydride, which hydrolyzes in the acidic lysosomal environment to allow pH-responsive release of DOX. The in vitro results demonstrate a pH-responsive drug release under different pH conditions. Furthermore, the targeting ability and therapeutic efficacy of the prodrug were assessed both in vitro and in vivo. The results demonstrate that FA-BSA-CAD prodrug selectively targeted tumor cells and tissue, with associated reduction in non-specific toxicity to the normal cells. More importantly, the therapeutic efficacy of the prodrug for FA-positive tumors increased compared to the non-conjuagted DOX.
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| Authors | Changli Du, Dawei Deng, Lingling Shan, Shunan Wan, Jie Cao, Junmei Tian, Samuel Achilefu, Yueqing Gu |
| Journal | Biomaterials (Biomaterials) Vol. 34 Issue 12 Pg. 3087-97 (Apr 2013) ISSN: 1878-5905 [Electronic] Netherlands |
| PMID | 23374705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
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