Bax Bridget E
Molecular and Clinical Sciences, St. George's, University of London, London SW17 0RE, UK.
Pharmaceutics. 2020 May 8;12(5):435. doi: 10.3390/pharmaceutics12050435.
Therapeutic enzymes are administered for the treatment of a wide variety of diseases. They exert their effects through binding with a high affinity and specificity to disease-causing substrates to catalyze their conversion to a non-noxious product, to induce an advantageous physiological change. However, the metabolic and clinical efficacies of parenterally or intramuscularly administered therapeutic enzymes are very often limited by short circulatory half-lives and hypersensitive and immunogenic reactions. Over the past five decades, the erythrocyte carrier has been extensively studied as a strategy for overcoming these limitations and increasing therapeutic efficacy. This review examines the rationale for the different therapeutic strategies that have been applied to erythrocyte-mediated enzyme therapy. These strategies include their application as circulating bioreactors, targeting the monocyte-macrophage system, the coupling of enzymes to the surface of the erythrocyte and the engineering of CD34 hematopoietic precursor cells for the expression of therapeutic enzymes. An overview of the diverse biomedical applications for which they have been investigated is also provided, including the detoxification of exogenous chemicals, thrombolytic therapy, enzyme replacement therapy for metabolic diseases and antitumor therapy.
治疗性酶被用于治疗多种疾病。它们通过与致病底物以高亲和力和特异性结合来发挥作用，催化其转化为无害产物，从而诱导有利的生理变化。然而，经肠胃外或肌肉注射给药的治疗性酶的代谢和临床疗效常常受到循环半衰期短以及超敏和免疫原性反应的限制。在过去的五十年里，红细胞载体作为克服这些限制并提高治疗效果的一种策略得到了广泛研究。本综述探讨了应用于红细胞介导的酶疗法的不同治疗策略的基本原理。这些策略包括将其用作循环生物反应器、靶向单核细胞 - 巨噬细胞系统、将酶偶联到红细胞表面以及对CD34造血前体细胞进行工程改造以表达治疗性酶。还提供了对已针对其进行研究的各种生物医学应用的概述，包括外源化学物质的解毒、溶栓治疗、代谢疾病的酶替代疗法和抗肿瘤治疗。
