Department of Biopharmaceutical Engineering, Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 38066, South Korea.
Colloids Surf B Biointerfaces. 2023 Jun;226:113335. doi: 10.1016/j.colsurfb.2023.113335. Epub 2023 May 3.
Glucose oxidase (GOD) exerts anticancer effects by producing hydrogen peroxide (HO). However, the use of GOD is limited by its short half-life and low stability. Systemic HO production following systemic absorption of GOD can also cause serious toxicity. GOD-conjugated bovine serum albumin nanoparticles (GOD-BSA NPs) may be useful for overcoming these limitations. Here, bioorthogonal copper-free click chemistry was employed to develop GOD-BSA NPs that are non-toxic and biodegradable and can effectively and rapidly conjugate proteins. These NPs retained their activity, unlike conventional albumin NPs. NPs using dibenzyl cyclooctyne (DBCO)-modified albumin, azide-modified albumin, and azide-modified GOD were fabricated in 10 min. After intratumoral administration, GOD-BSA NPs remained in the tumor for a longer period and displayed better anticancer activity than the effects of GOD alone. GOD-BSA NPs were approximately 240 nm in size and inhibited tumor growth to 40 mm, whereas tumors treated with phosphate-buffered saline or albumin NPs had sizes of 1673 and 1578 mm, respectively. GOD-BSA NPs prepared using click chemistry may be useful as a drug delivery system for protein enzymes.
葡萄糖氧化酶（GOD）通过产生过氧化氢（HO）发挥抗癌作用。然而，由于其半衰期短和稳定性低，GOD 的使用受到限制。GOD 经全身吸收后产生的系统性 HO 也会引起严重的毒性。GOD 结合牛血清白蛋白纳米颗粒（GOD-BSA NPs）可能有助于克服这些限制。在这里，采用生物正交的无铜点击化学来开发 GOD-BSA NPs，这些 NPs 具有非毒性、可生物降解性，并且可以有效地、快速地结合蛋白质。与传统的白蛋白 NPs 不同，这些 NPs 保留了其活性。使用二苄基环辛炔（DBCO）修饰的白蛋白、叠氮化物修饰的白蛋白和叠氮化物修饰的 GOD 制备 NPs 仅需 10 分钟。瘤内给药后，GOD-BSA NPs 在肿瘤中停留时间更长，表现出比单独使用 GOD 更好的抗癌活性。GOD-BSA NPs 的大小约为 240nm，可抑制肿瘤生长至 40mm，而用磷酸盐缓冲盐水或白蛋白 NPs 处理的肿瘤大小分别为 1673 和 1578mm。使用点击化学制备的 GOD-BSA NPs 可能可用作蛋白质酶的药物递送系统。
