pH-responsive dynamic organic nanocomposite hydrogels for enhanced local tumor combination therapy

A single drug therapeutic approach fails to sufficiently eliminate tumors in clinics, owing to the tumoral complexity and heterogeneity. The integration of chemotherapy with novel treatment modalities offers a promising synergistic strategy for enhancing therapeutic outcomes. Herein, we successfully develop pH-triggered dynamic organic nanocomposite hydrogels for enhanced local tumor combination therapy, which are prepared through incorporation of Cu_2-xSe nanoparticles (NPs) and lipophilic mixture (OPC) including orthoester compound, polycaprolactone and carboplatin into imine-crosslinked polysaccharide-based hydrogels. The dynamic imine linkages endow the hydrogels with favorable injectability and self-adaptability as well as tumoral extracellular pH-triggered degradation. OPC can enhance drug escape from hydrogels, tumor penetration and pH-responsive prolonged and sustained release of the drug. Cu_2-xSe NPs endow the hydrogels with photothermal therapy (PTT), photodynamic therapy (PDT) and chemo-dynamic therapy (CDT). These superior physicochemical properties result in significant tumor growth inhibition while decreasing side effect on normal tissues. Therefore, the pH-responsive dynamic organic nanocomposite hydrogels have great potential for local tumor therapy in clinics.