NIR-II light-modulated thermosensitive hydrogel for light-triggered cisplatin release and repeatable chemo-photothermal therapy

Cisplatin is one of the most effective chemotherapeutic agents, although its clinical use is limited by severe nephrotoxicity. Multifunctional platform for spatiotemporally controlled delivery of cisplatin and multimodal synergistic therapy is highly desirable in antitumor research. Herein, for the first time, an injectable, NIR-II light-modulated and thermosensitive hydrogel is synthesized through supramolecular self-assembly of a conjugated polymer and α-cyclodextrin. This hydrogel intrinsically features NIR responsive characteristics and thermo-responsive properties. The conjugated polymer (poly(N-phenylglycine)) not only tethers the poly(ethylene glycol) chains to enable the hydrogel formation, but also serves as the NIR-absorbing mediators. Accordingly, one particular benefit of this hydrogel is that its building blocks absorb NIR-II light and mediate the photothermal conversion itself, offering the important advantage of a prolonged retention time and thus permitting repeatable treatment upon a single-injection of this hydrogel. Under NIR-II laser irradiation, the localized photothermal effect not only ablates the highly metastatic triple-negative breast cancer (TNBC), but also triggers the on-demand cisplatin release through the thermo-responsive gel–sol transition, thus resulting in enhanced antitumor activity and reduced off-target toxicity. This work not only provides a novel multifunctional platform for NIR-triggered cisplatin release and chemo-photothermal combination therapy, but also presents a promising strategy for the rational design of NIR light-responsive hydrogels for the intervention of highly aggressive cancers.