Abstract To date, the encapsulation of therapeutic enzymes in a protective matrix is an optimized strategy for the maintenance of their stability, facilitating their clinical application. However, the stability and activity of therapeutic enzymes are often in tension with each other. A rigid protective matrix may effectively maintain the stability of therapeutic enzymes, but it can reduce the diffusion of substrates toward the therapeutic enzyme active site, dramatically affecting their catalytic efficiency. Here, we exploited a kind of nanogels by in situ polymerization on the arginine deiminase (ADI) surface with 3-acrylamido-phenylboronic acid (APBA) monomer. These nanogels efficiently improved the thermal stability (25–75℃), the pH stability (pH 1–13), and protease (trypsin) stability of ADI due to the strong rigidity of the surface poly(APBA) shell. And even after 60 days of storage, ∼60% of the activity of ADI encapsulated by nanogels remained. Furthermore, ADI encapsulated by nanogels could efficiently degrade arginine to increase the ratio of citrulline to arginine in mice plasma. That is because autologous glucose binds with APBA leading to the hydrophilicity increase of nanogels, and then, the arginine molecules can readily diffuse toward the encapsulated ADI. This nanogel platform eases the tension between the stability and activity of therapeutic enzymes. The resulting nanogels can efficiently maintain the in vitro stability and the in vivo activity of therapeutic enzymes, facilitating the exploitation of new therapeutic enzyme formulations, which can be transported and stored in vitro for a long time and be applied effectively in vivo.

中文翻译：

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葡萄糖响应性纳米凝胶有效保持治疗酶的稳定性和活性

摘要 迄今为止，将治疗性酶封装在保护性基质中是维持其稳定性、促进其临床应用的优化策略。然而，治疗性酶的稳定性和活性往往相互矛盾。刚性保护基质可以有效地维持治疗性酶的稳定性，但会减少底物向治疗性酶活性位点的扩散，从而显着影响其催化效率。在这里，我们通过在精氨酸脱亚胺酶 (ADI) 表面与 3-丙烯酰胺-苯基硼酸 (APBA) 单体进行原位聚合，开发了一种纳米凝胶。这些纳米凝胶有效地提高了热稳定性（25–75℃）、pH 稳定性（pH 1–13）、由于表面聚（APBA）壳的强刚性，ADI 的蛋白酶（胰蛋白酶）稳定性。即使在储存 60 天后，被纳米凝胶包裹的 ADI 的 60% 的活性仍然存在。此外，纳米凝胶包裹的 ADI 可以有效降解精氨酸，从而增加小鼠血浆中瓜氨酸与精氨酸的比例。这是因为自体葡萄糖与 APBA 结合导致纳米凝胶的亲水性增加，然后精氨酸分子可以很容易地向封装的 ADI 扩散。这种纳米凝胶平台缓解了治疗性酶的稳定性和活性之间的紧张关系。由此产生的纳米凝胶可以有效地维持治疗性酶的体外稳定性和体内活性，促进新的治疗性酶制剂的开发，