Pierigè Francesca, Bigini Noemi, Rossi Luigia, Magnani Mauro
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017 Sep;9(5). doi: 10.1002/wnan.1454. Epub 2017 Jan 24.
Recently optimized technologies that permit the reversible opening of nanopores across the red blood cell membrane, give the extraordinary opportunity for reengineering human erythrocytes to be used in different biomedical applications, both for therapeutic and diagnostic purposes. Engineered erythrocytes have been exploited as a system for the controlled release of drugs in circulation upon encapsulation of prodrugs or small molecules; as bioreactors when they are endowed of recombinant enzymes able to catalyze the conversion of toxic metabolite into inert products; as drug targeting system for the delivery of compounds to the reticuloendothelial system inducing proper senescent signals on the drug-loaded erythrocyte membrane; as carrier of contrasting agents for diagnostic procedures. Preclinical development of these different applications has taken advantage from the use of proper animal models whose erythrocytes can be reengineered as the human ones or the encapsulation procedures can be adapted on the basis of their specific erythrocyte biological features. Successful results, obtained both in vitro and in preclinical studies, have prompted several clinicians to start pilot clinical investigations in different conditions and some new companies to start the industrialization of selected loading technologies and to initiate clinical development programs. This short review summarizes the key features that, to the best of our knowledge, have been crucial to advance the products toward regulatory clinical approval making reengineering of erythrocytes a modality to treat patients with limited or absent therapeutic options. WIREs Nanomed Nanobiotechnol 2017, 9:e1454. doi: 10.1002/wnan.1454 For further resources related to this article, please visit the WIREs website.
最近优化的技术能够使纳米孔可逆地穿过红细胞膜，这为改造人类红细胞提供了绝佳机会，使其可用于不同的生物医学应用，包括治疗和诊断目的。工程化红细胞已被用作一种系统，用于在包封前药或小分子后在循环中控制药物释放；当赋予其能够催化有毒代谢物转化为惰性产物的重组酶时，可作为生物反应器；作为药物靶向系统，用于将化合物递送至网状内皮系统，在载药红细胞膜上诱导适当的衰老信号；作为诊断程序中造影剂的载体。这些不同应用的临床前开发得益于使用合适的动物模型，其红细胞可像人类红细胞一样进行改造，或者包封程序可根据其特定的红细胞生物学特征进行调整。在体外和临床前研究中均取得的成功结果促使几位临床医生在不同情况下开展试点临床研究，并促使一些新公司开始选定加载技术的产业化，并启动临床开发项目。这篇简短的综述总结了据我们所知对推动产品获得监管临床批准至关重要的关键特征，使红细胞改造成为治疗选择有限或没有治疗选择的患者的一种方式。WIREs Nanomed Nanobiotechnol 2017, 9:e1454. doi: 10.1002/wnan.1454 有关本文的更多资源，请访问WIREs网站。
