The novel dual targeted nanoparticles loaded with doxorubicin (DOX) and magnetic nanoparticles (MNPs) were prepared for treatment of breast cancer. Nanoparticles were produced by a layer-by-layer technique and functionalized with a bioconjugate of chitosan-poly(methyl vinyl ether maleic acid)(PMVMA)-LHRH to target LHRH receptors. The successful production of chitosan-PMVMA copolymer and its conjugation to LHRH was confirmed by FTIR and 1HNMR spectroscopy. Capillary electrophoresis analysis showed 72.51% LHRH conjugation efficiency. Transmission electron microscopy and thermogravimetric analysis showed the entrapment of the MNPs in the core of the nanoparticles and vibrating sample magnetometery confirmed their paramagnetic properties. The iron content of nanoparticles determined by inductively coupled plasma optical emission spectrometry showed to be between 3.5-84%. Particle size, zeta potential, drug entrapment and release efficiency of the nanoparticles were 88.1-182.6nm, 10-30mV, 62.3-87.6% and 79.8-83.4%, respectively. No significant protein binding was seen by nanoparticles. The MTT assay showed in LHRH positive cells of MCF-7 the IC50 of the drug reduced to about 2 fold compared to the free drug. By saturation of LHRH receptors the viable MCF7 cells increased significantly after exposure with the targeted nanoparticles. Therefore, the cellular uptake of the nanoparticles might be done by active endocytosis through the LHRH receptors.
Keywords: Breast cancer; Chitosan-poly(methyl vinyl maleic acid); Doxorubicin hydrochloride; LHRH; Magnetic nanoparticles.
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