Multifunctionalized Protein-Based Drug Delivery System for Inhibition of Tumor Growth and Progression

To improve the bioavailability of hydrophobic drugs and realize tumor targeting therapeutic actions efficiently, a nanosized multifunctional protein-based drug delivery system was constructed by self-assembly in a facile manner. Negatively charged cRGD-conjugated bovine serum albumin (cRGD-BSA) loaded with a hydrophobic antitumor drug (curcumin, CUR) was complexed with electropositive protamine sulfate (PS) via electroattractive forces to form CUR@cRGD-BSA/PS nanoparticles. Flow cytometry and confocal microscopy show that the multifunctional CUR@cRGD-BSA/PS nanoparticles lead to significantly increased intracellular drug accumulation in tumor cells owing to the tumor specific affinity of cRGD ligands as well as the membrane translocating property of PS. As a result, the multifunctional protein-based delivery system (CUR@cRGD-BSA/PS) exhibits an apparently enhanced inhibitory efficiency on malignant cells as compared with free CUR and the monofunctional delivery system (CUR@cRGD-BSA). More importantly, the expression of proteins (Bcl-2, cyclin D1, β-catenin, c-Myc, and MMP-9) involved in cancer development in the tumor cells treated by CUR@cRGD-BSA/PS is dramatically downregulated, implying the functional protein-based drug delivery system can effectively prevent tumor progression. Our investigation gives insight into the construction of multifunctional protein-based delivery carriers for tumor targeting delivery of hydrophobic drugs.