Tremendous attention in biomedical sciences has been given to nanoparticles in the past decades. Therapeutic agents can be linked to nanoparticles to enhance their selectivity and targeted delivery while impeding systemic toxicity and efficacy loss. Titanium dioxide nanoparticles (TiNPs) owe its rise in biomedical sciences to its versatile applicability and inherent properties. Structural modifications can improve TiNP’s antibacterial impact. Nitric oxide (NO) is proven to play a pivotal role in many of the human body’s physiological responses as a small gaseous signaling agent. The antibacterial efficacy of NO against a broad-spectrum of bacterial strains is well-established. For the first time, S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor molecule, was covalently immobilized on TiNPs. The hydroxyl-rich surface of TiNPs were surface silanized with 3-Aminopropyl triethoxysilane. Thiolactone chemistry enabled covalent linkage of the precursor N-acetyl-d-penicillamine to link to the amines. Finally, tert-butyl nitrite was used for nitrosation reaction leading to the NO-rich SNAP conjugation to the surface. Conjugation efficiency was assessed through quantitative (ninhydrin, Ellman’s, and real-time nitric oxide release) and qualitative (Fourier-transform infrared, energy dispersive X-ray spectroscopy, and zeta potential) assays. Total NO load was measured to be 127.55 ± 4.68 nmol/mg using a gold-standard chemiluminescence NO analyzer. NO payload can be released under physiological conditions for up to 20 h. SNAP conjugated TiNP’s antimicrobial efficacy was shown to be concentration-dependent. At 5 mg/mL, more than 99.99% and 99.48% reduction in viable Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, respectively were observed after 24 h exposure. No significant cytotoxicity was observed against 3T3 mouse fibroblast cells at the same concentration using CCK-8, particles’ leachate assay. SNAP-TiNP was shown to be a very promising, novel, and versatile nanoparticle that can significantly impact the usage of TiNPs in a wide variety of applications, such as biomaterial coatings, tissue engineering scaffolds, or wound dressings.

Nitric oxide-releasing titanium dioxide nanoparticles as a versatile and robust antibacterial agent

ACS Fall 2021

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