ABSTRACT

Introduction

Autophagy is a critical housekeeping pathway to remove toxic protein aggregates, damaged organelles, providing cells with bioenergetic substrates needed to survive under adverse conditions. Since altered autophagy is associated with diverse diseases, its pharmacological modulation is considered of therapeutic interest. Nanomedicines may reduce the toxicity and improve the activity of toxic autophagy modulatory drugs (amd).

Areas covered

The status of the most relevant anti-tumor, anti-inflammatory, and anti-infectious treatments mediated by autophagy modulatory nanomedicines (amN) published in the last 5 years is discussed.

Expert opinion

Antitumor and anti-inflammatory treatments may be improved by administering amN for selective, massive, and targeted delivery of amd to diseased tissues. The use of amN as antimicrobial agent remains almost underexploited. Assessing the effect of amN on the complex autophagy machinery operating under different basal diseases, however, is not a trivial task. Besides structural reproducibility, nanomedicines must grant higher efficiency, and lower adverse effects than conventional medication. Simplicity of design, carefully chosen (scalable) preparation techniques, and rigorous monitoring of preclinical efficacy and nanotoxicity will improve the chances of clinical success. Currently, available data are not sufficient to envisage a fast-succeeding translation. Application of quality by design criteria would help to reach such milestones.

中文翻译：

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临床前自噬调节纳米药物：挑战巨大，进展缓慢

摘要

介绍

自噬是去除有毒蛋白质聚集体、受损细胞器的关键管家途径，为细胞提供在不利条件下生存所需的生物能底物。由于改变的自噬与多种疾病有关，因此其药理学调节被认为具有治疗意义。纳米药物可以降低毒性自噬调节药物（amd）的毒性并提高其活性。

覆盖区域

讨论了过去 5 年发表的由自噬调节纳米药物 (amN) 介导的最相关的抗肿瘤、抗炎和抗感染治疗的现状。

专家意见

通过使用 amN 选择性、大量和有针对性地递送amd可以改善抗肿瘤和抗炎治疗到病变组织。使用 amN 作为抗微生物剂仍然几乎没有得到充分利用。然而，评估 amN 对在不同基础疾病下运行的复杂自噬机制的影响并非易事。除了结构可重复性，纳米药物必须比传统药物具有更高的效率和更低的副作用。设计的简单性、精心选择的（可扩展的）制备技术以及对临床前功效和纳米毒性的严格监测将提高临床成功的机会。目前，可用数据不足以设想快速成功的翻译。按设计标准应用质量将有助于达到这样的里程碑。