Development of biocompatible iron oxide-silicon oxide core-shell nanoparticles as subcellular delivery platform for glucosamine-6-phosphate synthase inhibitors - Publication - Bridge of Knowledge

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Development of biocompatible iron oxide-silicon oxide core-shell nanoparticles as subcellular delivery platform for glucosamine-6-phosphate synthase inhibitors

Abstract

In order to develop the preparation of iron oxide-silica coreshell nanoparticles (CSNPs), thesis deeply explores the cetyltrimethylammonium (CTA+) directed silica coating methods of the oleic-acid capped iron oxide nanoparticles (OA-IONPs) initialized under near-neutral pH conditions. It is demonstrated that the initial alkaline hydrolysis of ethyl acetate in the presence of CTA+ and OA-IONPs induces an unusual ligand exchange mechanism between oleic acid and in situ formed acetate ions. The acetate induced mechanism is shown to be catalysing the formation of ∼20-25 nm thick amorphous silica shells around the individual iron oxide nanoparticles resulting in highly mono-dispersed CSNPs. Synergetic effects of the iron oxide nanoparticle clusters (IONPCs) and the in situ formed CTAB vesicles encapsulating the silica precursors formed in high [CTAB]/[IONP] ratio conditions are demonstrated. Detailed electron energy-loss spectroscopy (EELS), Fourier transform-infrared (FT-IR), Raman and NMR spectroscopy further supports the micellar fusion mechanism behind the formation of CSNPs. Thesis further presents the superparamagnetic properties of aqueously well dispersible CSNPs prepared by reported nanoemulsion procedure. Measurement of the magnetic properties, confirming the superparamagnetic nature of CSNPs by DC magnetometry and paramagnetic nature of the particles confirmed by AC magnetometry, are discussed in detail. In vitro biological activities of CSNP-GlcN-6-P inhibitor conjugates against human cervical cancer (HeLa), hypopharyngeal carcinoma (FaDu), human fibroblast (MSU1.1) cell lines and Candida albicans demonstrates that the human cells almost completely loose their viability in the presence of CSNP-GlcN-6-P inhibitor conjugates, whereas, the growth of Candida albicans is reduced by only 30%. Nevertheless, cellular internalization studies performed with polyethyleneglycol functionalized core-shell nanoparticles (OH-PEG-CSNPs) in the absence of GlcN-6-P inhibitors by TEM imaging evidences the excellent biocompatibility of OH-PEG-CSNPs. Biological TEM studies suggest that, elevated internalization of OHPEG-CSNPs by human cells in contrast to inefficient internalization by Candida albicans could be the explanation for ineffective inhibition of fungal cells. Overall, the thesis questions the validity and meaning of “biocompatibility” approach in nanoparticle formulations of antifungal agent.

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Category:
Thesis, nostrification
Type:
praca doktorska pracowników zatrudnionych w PG oraz studentów studium doktoranckiego
Language:
English
Publication year:
2018
Verified by:
Gdańsk University of Technology

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