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.

It is of vital importance to engineer the surface structures of carbon dots (CDs) to satisfy their practical biomedical applications, including imaging and treatment. In this work, one type of hyaluronic acid-derived CD (HA-CD) was synthesized via a facile one-step hydrothermal method using cancer cell-targeted HA as a precursor. The as-prepared HA-CDs were targeted actively toward CD44 receptor-overexpressing cancer cells because a partial HA structure remained on the HA-CD surface. Beyond this, HA-CDs can act as a novel photosensitizer, because they can generate O₂˙⁻ under 650 nm laser irradiation, and they also exhibit excellent blue photoluminescence emission. The in vitro results revealed that HA-CDs imaged selectively CD44-overexpressing cancer cells and inhibited their growth under 650 nm laser irradiation. Thus, HA-CDs can serve as a promising self-targeted imaging-guided photodynamic therapy (PDT) agent for cancer. The present research provides a promising new method to simply construct multifunctional CD-based targeted phototheranostic systems.