Nitric Oxide Release and Antibacterial Efficacy Analyses of S-Nitroso-N-Acetyl-Penicillamine Conjugated to Titanium Dioxide Nanoparticles

Abstract

Therapeutic agents can be linked to nanoparticles to fortify their selectivity and targeted delivery while impeding systemic toxicity and efficacy loss. Titanium dioxide nanoparticles (TiNPs) owe their rise in biomedical sciences to their versatile applicability, although the lack of inherent antibacterial properties limits its application and necessitates the addition of bactericidal agents along with TiNPs. Structural modifications can improve TiNP’s antibacterial impact. The antibacterial efficacy of nitric oxide (NO) against a broad spectrum of bacterial strains is well established. For the first time, S-nitroso-N-acetylpenicillamine (SNAP), an NO donor molecule, was covalently immobilized on TiNPs to form the NO-releasing TiNP–SNAP nanoparticles. The TiNPs were silanized with 3-aminopropyl triethoxysilane, and N-acetyl-d-penicillamine was grafted to them via an amide bond. The nitrosation was carried out by t-butyl nitrite to conjugate the NO-rich SNAP moiety to the surface. The total NO immobilization was measured to be 127.55 ± 4.68 nmol mg–1 using the gold standard chemiluminescence NO analyzer. The NO payload can be released from the TiNP–SNAP under physiological conditions for up to 20 h. The TiNP–SNAP exhibited a concentration-dependent antimicrobial efficiency. At 5 mg mL–1, more than 99.99 and 99.70% reduction in viable Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, respectively, were observed. No significant cytotoxicity was observed against 3T3 mouse fibroblast cells at all the test concentrations determined by the CCK-8 assay. TiNP–SNAP is a promising 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.

S-Nitroso-N-acetylpenicillamine grafted silicone oil for antibacterial interface applications

“…75 Comparable results have been reported in the literature with NO-releasing materials that show decreased bactericidal efficiency against E. coli and other Gram-negative bacteria. 68,76…”

“…75 Comparable results have been reported in the literature with NO-releasing materials that show decreased bactericidal efficiency against E. coli and other Gramnegative bacteria. 68,76 Previous reports on SNAP-based biomaterials have demonstrated the antimicrobial effects against various pathogenic bacteria and fungus strains in medical device-related infections such as P. aeruginosa, S. epidermidis, and C. albicans. [77][78][79] Nevertheless, these prior studies involved either blending or impregnating the materials with NO donor SNAP, which are often challenged by leaching of the small molecule NO donors that delocalizes the NO release from the polymer surfaces.…”

Surface modification of TiO2 nanoparticles with organic molecules and their biological applications

“…For this goal, TiO 2 NPs were first silanized with APTES, and then N -acetyl- d -penicillamine was grafted to them via an amide bond. 54 TiO 2 NPs@APTES-SNAP showed antimicrobial properties (5 mg mL −1 ) on both Gram-positive Staphylococcus aureus ( S. aureus ) and Gram-negative Escherichia coli ( E. coli) bacteria and the biocompatibility on 3T3 mouse fibroblast cells, at all tested concentrations. Dymerska et al proposed a nanocomposite made from ultrasmall TiO 2 NPs embedded in a silica/carbon matrix.…”

Fe‐containing metal–organic framework with D‐penicillamine for cancer‐specific hydrogen peroxide generation and enhanced chemodynamic therapy

“…According to the DLS analysis (Figure 1f,g), the average particle sizes of NH 2 ‐MIL‐101(Fe), NH 2 ‐MIL‐101(Fe)/ d ‐pen, and NH 2 ‐MIL‐101(Fe)/CPT‐11 were 723, 756, and 766 nm, respectively. The surface charge of the NH 2 ‐MIL‐101(Fe) was 20.5 mV, which, however, decreased to 5.7 and 13.4 mV with the NH 2 ‐MIL‐101(Fe)/ d ‐pen and NH 2 ‐MIL‐101(Fe)/CPT‐11 as each of the loaded compounds was negatively charged 53,54 …”