Targeted Delivery of 5-fluorouracil with Monoclonal Antibody Modified Bovine Serum Albumin Nanoparticles

Document Type : Research article

Authors

1 Biotechnology Group, Chemical Engineering Faculty, Tarbiat Modares University, Tehran, Iran

2 Department of Immunology, School of Public Health, Tehran University of Medical Science, Tehran, Iran

3 Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran

Abstract

Herein, 1F2, an anti-HER2 monoclonal antibody (mAb), was covalently coupled to the surface of 5-Fluorouracil (5-FU) loaded bovine serum albumin (BSA) nanoparticles. Concerning two different crosslinkers for conjugation of 1F2, Maleimide-poly (ethylene glycol)-Succinimidyl carbonate (Mal-PEG5000-NHS) was selected due to its higher conjugation efficiency (23±4 %) obtained in comparison to N-succinimidyl 3-(2-Pyridyl Dithio) Propionate (SPDP) (8±2 %). A slight increase in the average particle size with a negligible prolongation of the 5-FU release was observed after 1F2 coupling. The 1F2-coupled 5-FU-loaded BSA nanoparticles interacted with nearly all HER2 receptors available on the surface of HER2-positive SKBR3 cells. No cellular uptake was observed for HER2-negative MCF7 cells. Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature. The in vitro cytotoxicity evaluation by MTT assay, demonstrated lower SKBR3 viability (50.7±9 %) after 5 hours contact with 1F2-coupled 5-FU-loaded BSA nanoparticles in comparison with the other control systems due to their cell attachment and internalization after washing. In addition, no significant toxicity was observed on MCF7 cells. This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.

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Iranian Journal of Pharmaceutical Research
Volume 14, Issue 2 - Serial Number 2
Spring 2015
Pages 395-405

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