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.