Biomimetic TME-Responsive Nanotheranostics for Precise NIR-II Ratiometric Photoacoustic Imaging and Synergistic
Xin Li1, Hongrui Qiu2, Lik Hang Hugo Tse1
1Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Abstract:
The complex immunosuppressive microenvironment of triple-negative breast cancer (TNBC) remains a major obstacle in attaining long-term clinical success and halting metastatic progression. To address this, the rational design of tumor microenvironment (TME)-responsive nanotheranostics is crucial for converting 'cold' tumors into 'hot' ones through synchronized imaging and precision therapy. Herein, we present a biomimetic, stimuli-activatable assembly (Au/Ag@HMON-NLG@CCM) utilizing a H2O2-responsive Au/Ag core to facilitate NIR-II ratiometric photoacoustic (PA) detection and thermal ablation. By encapsulating the IDO inhibitor NLG919 within a hollow mesoporous organosilica (HMON) shell and coating with cancer cell membrane (CCM), the system achieves superior tumor-targeting and synergistic immuno-photothermal effects. Specifically, TME-overexpressed H2O2-induces the oxidative degradation of the Ag, shifting the absorption into the NIR-II window to enable robust ratiometric PA visualization and efficient PTT (η = 42.8%). The resulting hyperthermia triggers immunogenic cell death (ICD) to initiate antigen release, while NLG919-mediated IDO1 blockade alleviates local immunosuppression, collectively remodeling the 'cold' TME. In bilateral tumor models, this integrated strategy effectively suppresses both primary lesions and distant metastases, demonstrating a potent systemic abscopal effect and durable antitumor immunity. Overall, this multifunctional nanoplatform provides a transformative strategy for NIR-II-guided precision medicine, offering a robust approach to eradicating metastatic and immunosuppressive malignancies.
