Photo synthesis of protein-based drug-delivery nanoparticles for active tumor targeting

Recently, nanometer-sized drug-delivery systems (DDSs) with an active targeting function to tumor sites have been cinfirmed to have great efficiency for cancer chemotherapy. However, the use of complicated modification techniques and the poor graft efficiency of the targeting ligands on the surface of the DDS have largely limited the application of most of the nano-DDSs. Especially for protein-based nano-DDSs, grafting of targeting ligands often requires genetic modification of the protein sequences, which is laborious and inefficient. Here, we present a novel method to photo synthesize a protein-based drug-delivery system with an active targeting function to tumor sites. The disulfide bonds in protein bovine α-lactalbumin (BLA) can be ruptured by controlled UV illumination, which triggers the formation of nano-sized protein aggregates and releases free thiol groups for the modification of the active targeting ligand of circular RGD peptide. Moreover, we demonstrated that the anti-cancer drug doxorubicin (DOX) can be loaded onto the protein-based DDS during the photo synthesis step. The synthesis approach is very convenient and cost-effective and can be accomplished under physiological conditions. Both in vitro and in vivo experiments validate that this DDS system possesses a much greater drug-delivery efficiency to the tumor sites and a better inhibition capability of tumor growth than the unmodified counterparts. This novel drug-delivery system can find broad applications in cancer chemotherapy. Moreover, our synthetic strategy can be easily extended to other disulfide-containing proteins and greatly expand the tool-box of protein-based DDSs for active targeting.