Multimodal imaging-guided NIR-II photo-gas nanoplatform amplifies PD-1 blockade for synergistic TNBC therapy.

RATIONALE: Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes due to its poor immunogenicity and resistance to systemic therapies.

METHODS

Here, we report a multifunctional NIR-II light-triggered theranostic nanoplatform, termed LQPO, that integrates liposome, Ti3C2 quantum dots (QDs), perfluorohexane (PFH), and ozone to enable multimodal imaging-guided photo-gas synergistic therapy. The QDs, embedded within the liposomal bilayer, act as highly efficient NIR-II photothermal transducers, while the PFH core serves as a liquid-gas phase-change medium capable of dissolving and releasing ozone under localized heating.

RESULTS

Upon NIR-II irradiation, LQPO produced strong photothermal and photoacoustic signals for real-time photoacoustic (PA) and contrast-enhanced ultrasound (CEUS) imaging, accompanied by vaporization of the PFH core and burst release of ozone. This spatiotemporally coordinated cascade induced potent oxidative stress and hyperthermia, synergistically driving GSDME-dependent pyroptosis and immunogenic cell death (ICD). The resulting "in situ vaccination" effect remodeled the tumor immune microenvironment and primed tumors for PD-1 blockade therapy. In vivo, NIR-II-activated LQPO achieved efficient tumor accumulation, strong PA/CEUS imaging contrast, and pronounced inhibition of both primary and abscopal tumors when combined with αPD-1 therapy. No significant systemic toxicity was observed, confirming its favorable biosafety.

CONCLUSIONS

Overall, this study establishes a single-laser-activated nanoplatform that unifies real-time multimodal imaging and photo-gas synergistic therapy, and converts localized treatment into a systemic antitumor immune response upon integration with checkpoint inhibition.