Locally injectable visible light-cured carboxymethyl chitosan hydrogels with indocyanine green-methyl-β-cyclodextrin for breast cancer phototherapy

Chemotherapy is the main therapy for triple-negative breast cancer (TNBC) but causes severe systemic toxicity. A hydrogel system that can be injected into the tumor along with photothermal/photodynamic combination therapy can potentially overcome systemic toxicity. Herein, we developed visible light-cured carboxymethyl chitosan methacrylate (CMCSMA) hydrogels containing an indocyanine green-methyl-β-cyclodextrin inclusion complex (ICG-ic-CD) as an injectable therapy for photo-triggered TNBC therapy. In vitro cell viability results from the inclusion complex of ICG and Me-βCD, which improves photostability and protects against light-induced degradation, revealed that 200 μg/mL ICG-ic-CD (ICG₂₀₀-ic-CD) hydrogel possessed good biocompatibility and had a photo-triggered TNBC therapeutic effect. In addition, various CMCSMA/ICG₂₀₀-ic-CD hydrogels demonstrated superior photothermal/photodynamic combination therapy in vitro and in vivo. These findings suggest that hydrogels composed of CMCSMA and 200 μg/mL of ICG-ic-CD (CMCSMA/ICG₂₀₀-ic-CD) possess an optimal crosslinking density that enables facile injection and effective diffusion of the ICG-ic-CD into tumor tissue. Moreover, the visible light-cured CMCSMA hydrogel system described here holds promise as a versatile local drug delivery platform for various cancer treatments, including chemotherapy, hormone therapy, and gene therapy, as the loading and release of drugs and biomolecules can be effectively controlled using this system.