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

Paper ID Volume ID Publish Year Pages File Format Full-Text
6273 471 2013 11 PDF Available
Title
A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery
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.

Keywords
Doxorubicin; pH-sensitive; Folic acid; Bovine serum albumin; Targeting; Therapeutic effect
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A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 12, April 2013, Pages 3087–3097
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us