Use of biotin targeted methotrexate-human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

Int J Nanomedicine. 2011:6:1863-74. doi: 10.2147/IJN.S23949. Epub 2011 Sep 8.


Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%.

Keywords: biotin; conjugates; human serum albumin; in vivo anticancer delivery; methotrexate; targeted drug delivery.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biotin / administration & dosage*
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Methotrexate / administration & dosage*
  • Mice
  • Mice, Inbred BALB C
  • Nanoconjugates / administration & dosage*
  • Nanomedicine
  • Serum Albumin / administration & dosage


  • Antineoplastic Agents
  • Nanoconjugates
  • Serum Albumin
  • Biotin
  • Methotrexate