Wilson Brenda A, Ho Mengfei
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Curr Top Med Chem. 2014;14(18):2081-93. doi: 10.2174/1568026614666141022094517.
Delivering therapeutic cargos to specific cell types in vivo poses many technical challenges. There is currently a plethora of drug leads and therapies against numerous diseases, ranging from small molecule compounds to nucleic acids to peptides to proteins with varying binding or enzymatic functions. Many of these candidate therapies have documented potential for mitigating or reversing disease symptoms, if only a means for gaining access to the intracellular target were available. Recent advances in our understanding of the biology of cellular uptake and transport processes and the mode of action of bacterial protein toxins have accelerated the development of toxin-based cargo-delivery vehicle platforms. This review provides an updated survey of the status of available platforms for targeted delivery of therapeutic cargos, outlining various strategies that have been used to deliver different types of cargo into cells. Particular emphasis is placed on the application of toxin-based approaches, examining critical issues that have hampered realization of post-intoxication antitoxins against botulism.
在体内将治疗性载荷递送至特定细胞类型面临诸多技术挑战。目前，针对众多疾病有大量的药物先导物和疗法，从小分子化合物到核酸，再到具有不同结合或酶功能的肽和蛋白质。如果有一种能够进入细胞内靶点的方法，那么这些候选疗法中的许多都已证明有减轻或逆转疾病症状的潜力。我们对细胞摄取和转运过程生物学以及细菌蛋白毒素作用模式的理解取得的最新进展，加速了基于毒素的载荷递送载体平台的开发。本综述对用于治疗性载荷靶向递送的现有平台的现状进行了更新调查，概述了用于将不同类型载荷递送至细胞的各种策略。特别强调了基于毒素方法的应用，审视了阻碍实现针对肉毒中毒的中毒后抗毒素的关键问题。
