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

Changli Du, Dawei Deng, Lingling Shan, Shunan Wan, Jie Cao, Junmei Tian, Samuel Achilefu, Yueqing Gu

Research output: Contribution to journalArticlepeer-review

203 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3087-3097
Number of pages11
Issue number12
StatePublished - Apr 2013
Externally publishedYes


  • Bovine serum albumin
  • Doxorubicin
  • Folic acid
  • PH-sensitive
  • Targeting
  • Therapeutic effect

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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