NIR-II Light-Modulated Smart Drug Delivery System Utilizing Drug-Gated Nanocomposite Hydrogel for Boosting Anticancer Efficacy

Boosting the effectiveness of cancer therapies by fine-tuning the tumor microenvironment has become a pivotal focus in modern cancer research. Nevertheless, the quest for impactful strategies in this regard is still ongoing. In this study, a drug-gated nanocomposite hydrogel was developed using polyglutamic acid-modified gold nanorods (AuNRs) and cisplatin (CDDP) to facilitate controlled drug release and augment localized combined antitumor effectiveness. CDDP not only serves as a cross-linking agent for creating the gel networks but also functions as a gating site for the controlled release of aPD-L1. This drug delivery system features a dual-action release mechanism, triggered by the endogenous chloride ions and enhanced by external near-infrared heating by AuNRs. Significantly, CDDP is clearly sensitized by this localized photothermal effect, which also results in tumor ablation. Additionally, the induction of immunogenic cell death through photothermal chemotherapy further potentiates the efficacy of aPD-L1-involved immune checkpoint blockade. The results demonstrated that this therapeutic gel scaffold has good antitumor effects that synergize with the effects of immune-mediated hyperthermic chemotherapy and show promising application of a local stimulus-responsive drug-delivery system.