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Original Article



Toxicity of thiolated silica nanoparticles modified with sulfobetaine methacrylate for potential use in chemotherapy drug conjugation

Abdulmajeed G. Almutary, Barbara J. S. Sanderson, Zahra Alhalili, Amanda V. Ellis.




Abstract

Nanoparticles (NPs) are promising substrates for the delivery of chemotherapy drugs to solid tumours. However, after injection these foreign bodies are often eliminated by the reticulo endothelial system (RES) within seconds or minutes. Previous studies overcome this issue by coating nano-drug carriers with a surfactant which extended the circulatory half-life of NPs and prevented opsonization. In the current study, thiolated silica nanoparticles (SiO2) were synthesized using the Stöber method then coated with low fouling zwitterionc sulfobetaine methacrylate (SBMA) using thiol-ene addition. Scanning electron micrographs (SEM) revealed monodispersed spherical particles with dynamic light scattering (DLS) showing a small increase in nanoparticle average diameter after modification with SBMA. Toxicity of the SiO2-SBMA nanoparticles (concentrations between 0.05-2.00mg/mL) was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and crystal violet assays on human colon carcinoma (Caco-2) and human skin keratinocytes (HaCaT) cell lines for 4, 24 and 48 h. The particles were also exposed to ultraviolet light (UV) to determine any possible degradation with zeta potential measurements revealing strongly anionic particles after 1 h UV light exposure. The SiO2-SBMA nanoparticles did not decrease the mitochondrial activity of Caco-2 or HaCaT cell lines using MTT assays; however, the LDH leakage increased and relative cell number decreased at 2.00 mg/mL and was clearly observed after the particles were exposed to UV light. These results indicate that concentrations ≤1.50 mg/mL of SiO2-SBMA low toxicity are biocompatible and show potential as a chemotherapy drug conjugate.

Key words: monodisperse silica; zwitterionc SBMA; HaCaT; Caco-2; MTT assay; LDH assay; size distribution






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