Facile preparation of biocompatible nanostructured lipid carrier with ultra-small size as a tumor-penetration delivery system.

Insufficient tumor penetration is one of the major obstacles for satisfactory cancer therapy. As a result, the ability to push the lower limits of size for nanoparticle platforms that have traditionally existed in larger forms is highly desirable. In our study, a facile solvent diffusion method was applied to prepare an ultra-small nanostructured lipid carrier (usNLC) which was capable of encapsulating hydrophobic molecules. Our results demonstrate that the as-prepared usNLC is composed of homogeneous particles with size around 25 nm. In addition to its preferable colloidal stability, negligible hemolysis as well as strong tumor homing property, the as-prepared usNLC shows preferable tumor penetration capacity both in vitro and in vivo. The paclitaxel (PTX) loaded usNLC shows comparable in vitro cytotoxicity on HepG2 cells and multicellular tumor spheroids to Taxol with the best in vivo anti-tumor efficacy, which all indicate its potential to be a promising candidate for cancer therapy.