Docetaxel immunonanocarriers as targeted delivery systems for HER2-positive tumor cells: preparation, characterization, and cytotoxicity studies
Mona Noori Koopaei1, Rassoul Dinarvand1,2, Mohsen Amini3, Hojatollah Rabbani4, Shaghayegh Emami4, Seyed Nasser Ostad5, Fatemeh Atyabi1,2
1Novel Drug Delivery Laboratory, Faculty of Pharmacy, 2Nanotechnology Research Center, 3Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Monoclonal Antibody Research Center, Avesina Research Institute, ACECR, Tehran, Iran; 5Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
Background: The objective of this study was to develop pegylated poly lactide-co-glycolide acid (PLGA) immunonanocarriers for targeting delivery of docetaxel to human breast cancer cells.
Methods: The polyethylene glycol (PEG) groups on the surface of the PLGA nanoparticles were functionalized using maleimide groups. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) antigens of cancer cells, used as the targeting moiety, was attached to the maleimide groups on the surface of pegylated PLGA nanoparticles. Nanoparticles prepared by a nanoprecipitation method were characterized for their size, size distribution, surface charge, surface morphology, drug-loading, and in vitro drug release profile.
Results: The average size of the trastuzumab-decorated nanoparticles was 254 ± 16.4 nm and their zeta potential was -11.5 ± 1.4 mV. The average size of the nontargeted PLGA nanoparticles was 183 ± 22 nm and their zeta potential was -2.6 ± 0.34 mV. The cellular uptake of nanoparticles was studied using both HER2-positive (SKBR3 and BT-474) and HER2-negative (Calu-6) cell lines.
Conclusion: The cytotoxicity of the immunonanocarriers against HER2-positive cell lines was significantly higher than that of nontargeted PLGA nanoparticles and free docetaxel.
Keywords: nanoparticles, drug targeting, immunonanocarriers, trastuzumab, docetaxel, PLGA, HER2 receptor
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