International Journal of Nanomedicine (May 2019)
Modified methods of nanoparticles synthesis in pH-sensitive nano-carriers production for doxorubicin delivery on MCF-7 breast cancer cell line
Abstract
Ahmed Hamidu,1,2 Ajat Mokrish,3 Rozaihan Mansor,3 Intan Shameha Abdul Razak,3 Abubakar Danmaigoro,3 Alhaji Zubair Jaji,3 Zuki Abu Bakar11Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; 2Department of Sciences and Engineering, Federal Polytechnic Mubi, Adamawa State, Nigeria; 3Department of Preclinical Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor 434000, Selangor, MalaysiaPurpose: Modified top-down procedure was successfully employed in the synthesis of aragonite nanoparticles (NPs) from cheaply available natural seawater cockle shells. This was with the aim of developing a pH-sensitive nano-carrier for effective delivery of doxorubicin (DOX) on MCF-7 breast cancer cell line.Methods: The shells were cleaned with banana pelts, ground using a mortar and pestle, and stirred vigorously on a rotary pulverizing blending machine in dodecyl dimethyl betane solution. This simple procedure avoids the use of stringent temperatures and unsafe chemicals associated with NP production. The synthesized NPs were loaded with DOX to form DOX-NPs. The free and DOX-loaded NPs were characterized for physicochemical properties using field emission scanning electron microscopy, transmission electron microscopy, zeta potential analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. The release profile, cytotoxicity, and cell uptake were evaluated.Results: NPs had an average diameter of 35.50 nm, 19.3% loading content, 97% encapsulation efficiency, and a surface potential and intensity of 19.1±3.9 mV and 100%, respectively. A slow and sustained pH-specific controlled discharge profile of DOX from DOX-NPs was observed, clearly showing apoptosis/necrosis induced by DOX-NPs through endocytosis. The DOX-NPs had IC50 values 1.829, 0.902, and 1.0377 μg/mL at 24, 48, and 72 hrs, while those of DOX alone were 0.475, 0.2483, and 0.0723 μg/mL, respectively. However, even at higher concentration, no apparent toxicity was observed with the NPs, revealing their compatibility with MCF-7 cells with a viability of 92%.Conclusions: The modified method of NPs synthesis suggests the tremendous potential of the NPs as pH-sensitive nano-carriers in cancer management because of their pH targeting ability toward cancerous cells.Keywords: apoptosis, biomedical application, CaCO3, nanoparticles and ultrastructure
