Preclinical autophagy modulatory nanomedicines: big challenges, slow advances

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).

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.

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.