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, the current nanoimprint lithography is a type of an additive nanofabrication method that has 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 also precisely prepare scalable nanocylinders with different length to diameter ratios. 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- and caveolae-mediated cell transport pathways and display increased cellular uptake, in comparison to 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.
Keywords: PLGA nanocylinders; controllable subtractive fabrication; enhanced cellular uptake; high drug-loading rate; improved cytotoxicity; long storage stability; nanoimprint lithography.