Preparation and size control of sub-100 nm pure nanodrugs

Pure nanodrugs (PNDs), nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes, and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile, and controllable strategy for preparing PNDs via an anodized aluminum oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anticancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.