Plasmonically Active Supramolecular Polymer–Metal–Organic Framework Hydrogel Nanocomposite for Localized Chemo-photothermal Therapy

Hydrogels are a three-dimensional cross-linked network of hydrophilic polymers, extensively used for biomedical, biotechnological, and pharmaceutical applications. The functionality of hydrogels could be enhanced by synthesizing hydrogel nanocomposites that can both enable controlled release of drugs in a cancerous microenvironment and near-infrared-induced localized heat generation for combined chemo-photothermal therapy (chemo-PTT), a potent anticancer therapeutic approach. Herein, we developed a plasmonically active hydrogel with carboxymethyl chitosan (CMC) as the supporting matrix cross-linked with ZIF8 nanoparticles and Mg2+. The ZIF8 nanoparticles were loaded in situ with ultrasmall gold nanoparticles (UsGNPs) and an anticancer drug curcumin for localized chemo-PTT. The plasmonic hydrogel (PHG) showed viscoelastic and self-healing properties governed by the supramolecular interaction between ZIF8 and CMC. The injectable PHG exhibited a photothermal conversion efficiency of ∼41%. Chemo-PTT with Cur-PHG effectively inhibited 4T1 breast cancer under both in vitro and in vivo conditions. The biocompatible PHG was found to release UsGNPs from tumor tissues post intratumoral injection followed by predominant distribution in the liver and kidney. Due to the size of UsGNPs (<5 nm), they were consistently detected in urine over the period of treatment confirming the overall degradable nature of PHG that delivers a localized outcome with negligible systemic toxicity.