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

Abstract

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%.

• Authors: Azade Taheri, Rassoul Dinarvand, Faranak Salman Nouri, Mohammad Reza Khorramizadeh, Atefeh Taheri Borougeni, Pooria Mansoori, Fatemeh Atyabi
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 6 Pg. 1863-74 ( 2011) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 21931482 (Publication Type: Evaluation Study, Journal Article)

Chemical References

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

Topics

• 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)