Hydrophobic Drug-Triggered Self-Assembly of Nanoparticlesfrom Silk-Elastin-Like Protein Polymers for Drug Delivery.

Silk-elastin-likeprotein polymers (SELPs) combine the mechanicaland biological properties of silk and elastin. These properties haveled to the development of various SELP-based materials for drug delivery.However, SELPs have rarely been developed into nanoparticles, partiallydue to the complicated fabrication procedures, nor assessed for potentialas an anticancer drug delivery system. We have recently constructeda series of SELPs (SE8Y, S2E8Y, and S4E8Y) with various ratios ofsilk to elastin blocks and described their capacity to form micellar-likenanoparticles upon thermal triggering. In this study, we demonstratethat doxorubicin, a hydrophobic antitumor drug, can efficiently triggerthe self-assembly of SE8Y (SELPs with silk to elastin ratio of 1:8)into uniform micellar-like nanoparticles. The drug can be loaded inthe SE8Y nanoparticles with an efficiency around 6.5% (65 ng doxorubicin/μgSE8Y), S2E8Y with 6%, and S4E8Y with 4%, respectively. In vitro studieswith HeLa cell lines demonstrate that the protein polymers are notcytotoxic (IC50> 200 μg/mL), while the doxorubicin-loadedSE8Y nanoparticles showed a 1.8-fold higher cytotoxicity than thefree drug. Confocal laser scanning microscopy (CLSM) and flow cytometryindicate significant uptake of the SE8Y nanoparticles by the cellsand suggest internalization of the nanoparticles through endocytosis.This study provides an all-aqueous, facile method to prepare nanoscale,drug-loaded SELPs packages with potential for tumor cell treatments. [ABSTRACT FROM AUTHOR]