SN-38-cholesterol NPs-loaded PDA NPs/agarose & pluronic F-127 hydrogel system for controlled chemo-phototherapy in tumor-localized treatment

Pluronic F-127 (PF-127) has low mechanical strength at low concentrations and a high gel-sol transition temperature at high concentrations, which limits its use as a controlled drug-release carrier. To address this issue while preserving the hydrogel's high biocompatibility, we developed a hydrogel system consisting of polydopamine nanoparticles (PDA NPs), agarose, and PF-127 (PDA/APF) in which agarose forms a secondary network and PDA NPs enhance hydrogen bonding in the network, thereby improving the mechanical strength and stability of the hydrogel. This modification prolonged the hydrogel's degradation period to approximately seven days and maintained gel-sol transition temperature at 59.0 °C. We incorporated SN-38-cholesterol NPs into the hydrogel system for sustained chemotherapy. Upon 808 nm near infrared (NIR) irradiation, the hydrogel system behaved as expected by releasing SN-38-cholesterol NPs through subsequent hydrogel degradation induced by the embedded PDA NPs. <i>In vivo</i> studies showed that the hydrogel system effectively inhibited tumor growth in mice following photothermal therapy with NIR light. The use of the PDA/APF hydrogel system is a promising strategy for controlled localized cancer therapy, combining chemotherapy and photothermal therapy for enhanced efficacy.