Light-Controlled Release of Therapeutic Proteins from Red Blood Cells,ACS Central Science

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Light-Controlled Release of Therapeutic Proteins from Red Blood Cells
ACS Central Science ( IF 12.7 ) Pub Date : 2020-12-09 , DOI: 10.1021/acscentsci.0c01151
Brianna M. Vickerman ₁ , Colin P. O’Banion ₂ , Xianming Tan ₃ , David. S. Lawrence _{1,

2,

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Affiliation

Protein therapeutics are a powerful class of drugs known for their selectivity and potency. However, the potential efficacy of these therapeutics is commonly offset by short circulatory half-lives and undesired action at otherwise healthy tissue. We describe herein a targeted protein delivery system that employs engineered red blood cells (RBCs) as carriers and light as the external trigger that promotes hemolysis and drug release. RBCs internally loaded with therapeutic proteins are readily surface modified with a dormant hemolytic peptide. The latter is activated via easily assigned wavelengths that extend into the optical window of tissue. We have demonstrated that photorelease transpires with spatiotemporal control and that the liberated proteins display the anticipated biological effects in vitro. Furthermore, we have confirmed targeted delivery of a clot-inducing enzyme in a mouse model. Finally, we anticipate that this strategy is not limited to RBC carriers but also should be applicable to nano- and microtransporters comprised of bilayer lipid membranes.

中文翻译：

光控制释放红细胞中治疗性蛋白质

蛋白质疗法是一类功能强大的药物，以其选择性和效力而著称。然而，这些疗法的潜在功效通常被短的循环半衰期和对其他健康组织的不良作用所抵消。我们在本文中描述了一种靶向蛋白质递送系统，该系统采用工程化红细胞（RBC）作为载体，而光作为促进溶血和药物释放的外部触发因素。内部装载有治疗性蛋白质的RBC容易被休眠的溶血肽进行表面修饰。后者通过容易分配的波长激活，该波长延伸到组织的光学窗口中。我们已经证明了具有时空控制的光释放膜和释放的蛋白在体外显示出预期的生物学效应。此外，我们已经证实在小鼠模型中靶向诱导凝块诱导酶。最后，我们预计该策略不仅限于RBC载体，还应适用于由双层脂质膜组成的纳米和微转运蛋白。

更新日期：2021-01-27

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