Construction of protein nanoparticles for targeted delivery of drugs to cancer cells

Protein nanoparticles (NPs) are potentially valuable carriers for drug delivery, because they are biocompatible, biodegradable, bioabsorbable, and can be easily designed to perform specific functions with high homogeneity when produced by genetic engineering. We constructed protein NPs based on genetically engineered elastin like polypeptides (ELPs) with a fused poly-aspartic acid tail (ELP-D) for use in drug delivery systems (DDSs). To ensure specific delivery of protein NPs, to cancer cells, targeting and internalizing molecules should be present on their surfaces. The iRGD peptide can activate integrin-dependent binding to cancer cells and neuropilin-1 (NRP-1)-dependent internalization into tumor tissues. In the present study, iRGD was genetically fused to the C-terminus of ELP-D to introduce active targeting and cell-penetrating functions to ELP-D NPs. The formation of NPs with iRGD moieties on their surfaces was examined, as well as their targeting ability. Anti-cancer drug paclitaxel (PTX)-loaded protein NPs with iRGD moieties were found to be effective in delivering the drug to cancer cells, becoming internalized into the cells, and inducing cell death.