Controllable Subtractive Nanoimprint Lithography for Precisely Fabricating Paclitaxel-loaded PLGA Nanocylinders to Enhance Anticancer Efficacy.

Nanoimprint lithography presents a new strategy for preparing uniform nanostructures with predefined sizes and shapes, and has the potential for developing nanosized drug delivery systems. However, current nanoimprint lithography is a type of additive nanofabrication method that has the limited potential due to its restricted template-dependent innate character. Herein, we have developed a novel subtractive UV-nanoimprint lithography (sUNL) for the scalable fabrication of PLGA nanostructures with variable sizes for the first time. sUNL can not only fabricate a variety of predefined nanostructures by simply utilizing different nanoimprint molds, but precisely prepare scalable nanocylinders with different ratios of length to diameter. Particularly, sUNL can fabricate paclitaxel-loaded PLGA nanocylinders (PTX-PLGA NCs) with high drug loading rate of 40% and long storage stability over a year. We demonstrate that PTX-PLGA NCs target clathrin-mediated and caveolae-mediated cell transport pathways, and display increased cellular uptake, in comparison of traditional PTX-loaded PLGA nanoparticles (PTX-PLGA NPs), leading to enhanced anticancer effects. Therefore, sUNL represents a promising nanofabrication method for efficiently developing predefined drug delivery systems.