Targeted Nanogels: A Versatile Platform for Drug Delivery to Tumors

While nanoparticle-based drug delivery formulations can improve the effectiveness and safety of certain anti-cancer drugs, many drugs, due to their chemical composition, are unsuitable for nanoparticle loading. Here, we describe a targeted nanogel drug delivery platform that can 1) encapsulate a wide range of drug chemotypes including: biological, small molecule, and cytotoxic agents 2) display targeting ligands and polymeric coatings on the surface, 3) enhance drug retention within the nanogel core after photo-crosslinking, and 4) retain therapeutic activity after lyophilization allowing for long term storage. For therapeutic studies, we utilized integrin αvβ3-targeted lipid-coated nanogels with crosslinked human serum albumin in the core for carrying therapeutic cargoes. These particles exhibited potent activity in tumor cell viability assays with drugs of distinct chemotype including: paclitaxel, docetaxel, bortezomib, 17-AAG, sorafenib, sunitinib, bosutinib, and dasatinib. Treatment of orthotopic breast and pancreas tumors in mice with taxane-loaded nanogels produced a 15-fold improvement in anti-tumor activity relative to Abraxane by blocking both primary tumor growth and spontaneous metastasis. With a modifiable surface and core, the lipid-coated nanogel represents a platform technology that can be easily adapted for specific drug delivery applications to treat a wide range of malignant diseases.