PNVCL-Based Multifunctional Nanogels Loaded with Curcumin, 5-Fluorouracil, and Gold Nanorods: Their Performance in Colon Cancer Cells

This study presents the development and evaluation of multifunctional, thermoresponsive nanogels based on poly(<i>N</i>-vinylcaprolactam-<i>co-N</i>-vinylpyrrolidone) (P(NVCL-<i>co</i>-NVP)) with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) shell and galactose (GAL) targeting ligand for colon cancer therapy. The nanogels were engineered to encapsulate two chemotherapeutic agents, curcumin (CUR) and 5-fluorouracil (5-FU), along with gold nanorods (GNRDs) to enable a synergistic chemo-photothermal treatment approach. These nanogels exhibit excellent biocompatibility and stability and a temperature-responsive drug release profile, leveraging the volume-phase transition temperature (VPTT) of the polymer network for controlled delivery. The inclusion of GNRDs permits efficient photothermal conversion upon near-infrared (NIR) irradiation, resulting in localized hyperthermia and, theoretically, improved cytotoxicity when combined with chemotherapeutics. In vitro studies on colon cancer cells demonstrated enhanced drug accumulation, photothermal ablation when the GNRD concentration was above a threshold, and superior antitumor efficacy of the CUR/5-FU-loaded systems. The effectiveness of the chemo/photothermal combination could not be demonstrated, possibly due to the low concentration of GNRD and/or the use of a single irradiation step only. This work highlights the potential of P(NVCL-<i>co</i>-NVP):PEGMA:GAL nanogels as versatile nanocarriers for combined chemo-photothermal therapy. A more effective chemo/photothermal combination for colon cancer treatment can be achieved through the optimization of the GNRD loading/irradiation dosage.