Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis.
Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis.
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DOI：
10.1016/j.addr.2016.01.016
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发表时间：
2016-07-01
影响因子：
16.1
通讯作者：
Deretic V
中科院分区：
文献类型：
--
作者：
Gupta A;Misra A;Deretic V
基于诱导自噬作为一种免疫效应，是一种很有前途的宿主定向化疗干预结核病（TB）的方法。在这里，我们考虑潜在的基于自噬的药物干预的优势和劣势。使用现有的诱导自噬的药物是一种选择，但考虑到自噬在大多数细胞、组织和器官中的广泛作用，它有局限性。因此，可能希望用于调节自噬的药物以靶向方式应用，例如递送到受影响的组织，感染巨噬细胞是一个明显的选择。本文综述了给药诱导结核分枝杆菌感染巨噬细胞自噬的优点和缺点。一种已经在模型中测试的选择是设计吸入输送到肺巨噬细胞的颗粒。讨论了药物的选择、药物释放动力学和细胞内停留时间、非靶细胞暴露和患者使用的可行性。我们在这里将这种（仍处于实验阶段的）方法称为“Track-II抗结核化疗”，这种方法是基于细胞室靶向、自噬、宿主导向的治疗方法。
One of the promising host-directed chemotherapeutic interventions in tuberculosis (TB) is based on inducing autophagy as an immune effector. Here we consider the strengths and weaknesses of potential autophagy-based pharmacological intervention. Using the existing drugs that induce autophagy is an option, but it has limitations given the broad role of autophagy in most cells, tissues, and organs. Thus, it may be desirable that the agent being used to modulate autophagy is applied in a targeted manner, e.g. delivered to affected tissues, with infected macrophages being an obvious choice. This review addresses the advantages and disadvantages of delivering drugs to induce autophagy in M. tuberculosis-infected macrophages. One option, already being tested in models, is to design particles for inhalation delivery to lung macrophages. The choice of drugs, drug release kinetics and intracellular residence times, non-target cell exposure and feasibility of use by patients is discussed. We term here this (still experimental) approach, of compartment-targeting, autophagy-based, host-directed therapy as “Track-II antituberculosis chemotherapy.”