Nitric Oxide Release and Antibacterial Efficacy Analyses of S-Nitroso-N-Acetyl-Penicillamine Conjugated to Titanium Dioxide Nanoparticles.
Nitric Oxide Release and Antibacterial Efficacy Analyses of S-Nitroso-N-Acetyl-Penicillamine Conjugated to Titanium Dioxide Nanoparticles.
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DOI：
10.1021/acsabm.2c00131
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发表时间：
2022-05-16
影响因子：
4.7
通讯作者：
Brisbois, Elizabeth J
中科院分区：
文献类型：
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作者：
Massoumi, Hamed;Kumar, Rajnish;Chug, Manjyot Kaur;Qian, Yun;Brisbois, Elizabeth J
治疗剂可以与纳米颗粒相连，以加强其选择性和靶向输送，同时防止全身毒性和疗效丧失。二氧化钛纳米颗粒(TiNPs)在生物医学领域的兴起归功于其广泛的适用性，尽管其固有的抗菌性能的缺乏限制了其应用，因此必须在TiNPs的基础上添加杀菌剂。结构修饰可以提高TiNP的抗菌效果。一氧化氮(NO)对广泛的细菌菌株具有良好的抗菌效果。首次将NO供体S-亚硝基-N-乙酰青霉胺(SNAP)共价固定在TiNPs上，形成了释放NO的TiNP-SNAP纳米粒子。用3-氨丙基三乙氧基硅烷对TiNPs进行硅烷化，并通过酰胺键将N-乙酰基青霉胺接枝到TiNPs上。亚硝化反应是由亚硝酸叔丁酯将富含NO的SNAP部分偶联到表面。用金标化学发光NO分析仪测得固定化NO总量为127.55±4.68nmol mg−1。在生理条件下，TiNP-SNAP可释放NO有效载荷长达20h。TiNP-SNAP具有浓度依赖性的抗菌效果。当−-1浓度为5 mg mL时，对活的革兰氏阳性金黄色葡萄球菌和革兰氏阴性杆菌的杀灭率分别大于99.99%和99.70%。CCK-8法测定的所有试验浓度对3T3小鼠成纤维细胞均无明显的细胞毒作用。TiNP-SNAP是一种前景看好、用途广泛的纳米粒子，可以显著影响TiNPs在生物材料涂层、组织工程支架或伤口敷料等广泛应用中的应用。
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.