Send to

Choose Destination
Biomaterials. 2013 Apr;34(12):3087-97. doi: 10.1016/j.biomaterials.2013.01.041. Epub 2013 Jan 29.

A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery.

Author information

State Key Laboratory of Natural Medicines, and Department of Biomedical Engineering, China Pharmaceutical University, Nanjing 210009, China.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center