用于全身解毒的酶治疗学。
Enzyme therapeutics for systemic detoxification.
机构信息
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
出版信息
Adv Drug Deliv Rev. 2015 Aug 1;90:24-39. doi: 10.1016/j.addr.2015.05.005. Epub 2015 May 13.
Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.
生命依赖于众多协同作用和正确运作的生化过程。某些物质会破坏这些过程，使生物体进入一种称为中毒的异常状态。管理中毒通常需要干预，这被称为解毒。解毒的数十年发展揭示了酶作为理想治疗剂和解毒剂的潜力，因为它们的高底物特异性和催化效率对于清除中毒物质而没有不良影响是必不可少的。然而，酶的固有缺点，包括低稳定性和高免疫原性，是主要的障碍，可以通过用专门设计的纳米载体来输送酶来克服。对蛋白质递送的广泛研究表明，有三种酶-纳米载体结构比其他结构更有希望用于系统解毒，包括包被在脂质体中的酶、聚合物-酶缀合物和聚合物包封的酶。本综述重点介绍了这些纳米结构的最新进展，并讨论了它们在系统解毒中的应用。还讨论了各种酶的治疗潜力以及在实现治疗酶有效递送上的相关挑战。
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