Reversible self-crosslinked polymer nanogels for stable delivery vehicles

Abstract

Research concerning drug delivery vehicles has attracted tremendous interest due to the potential for encapsulating insoluble and toxic hydrophobic drugs, inducing controlled release through relevant biomarkers and achieving selective delivery to target sites. Self-assembled systems such as polymeric micelles, dendrimers and liposomes have been widely studied because of their encapsulation capacity for water-insoluble guests and ability for simple modification through molecular design. Nanoscale vehicles for delivery have been of interest and extensively studied for two decades. However, the encapsulation stability of hydrophobic drug molecules in delivery vehicles and selective delivery into targeting disease cells is a potential hurdle for efficient delivery systems. Here, we demonstrate a simple and fast synthetic protocol of nanogels that shows high encapsulation stabilities. These nanogels can also be modified various targeting ligands for active targeting. We show that the targeting nanogels (T-NGs), which are prepared within 2 hours by a one-pot synthesis, exhibit very narrow size distributions and have the versatility of surface modification with cysteine-modified ligands including folic acid, cyclic arginine-glycine-aspartic acid (cRGD) peptide, and cell-penetrating peptide. T-NGs hold their payloads, undergo facilitated cell internalization by receptor-mediated uptake, and release their drug content inside cells due to the reducing intracellular environment. Selective cytotoxicity to cells, which have complementary receptors, is also demonstrated.