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.
Small (Weinheim an Der Bergstrasse, Germany)
|June 2, 2026
Summary
This study introduces a novel nanoplatform that converts cold tumors into hot ones for triple-negative breast cancer (TNBC) treatment. It uses advanced imaging and therapy to target tumors and reduce immunosuppression, effectively halting cancer progression.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) presents a complex immunosuppressive tumor microenvironment (TME), hindering effective treatment and leading to metastasis.
- Developing TME-responsive nanotheranostics is essential for converting 'cold' tumors into 'hot' ones via combined imaging and precision therapy.
Purpose of the Study:
- To design and evaluate a biomimetic, stimuli-activatable nanoplatform (Au/Ag@HMON-NLG@CCM) for enhanced TNBC therapy.
- To achieve synchronized NIR-II photoacoustic imaging and photothermal therapy (PTT) for precise treatment.
- To synergistically combine PTT with IDO1 inhibition to remodel the immunosuppressive TME and overcome treatment resistance.
Main Methods:
- Fabrication of a nanoplatform with a H2O2-responsive Au/Ag core, hollow mesoporous organosilica (HMON) shell encapsulating IDO inhibitor NLG919, and cancer cell membrane (CCM) coating.
- Utilizing H2O2-induced degradation of Ag for NIR-II ratiometric photoacoustic (PA) detection and PTT.
- Evaluating the synergistic immuno-photothermal effects, immunogenic cell death (ICD) induction, and IDO1 blockade in bilateral tumor models.
Main Results:
- The nanoplatform demonstrated efficient NIR-II PA imaging and PTT (η = 42.8%) triggered by TME-specific H2O2.
- The combined hyperthermia and NLG919 treatment effectively induced ICD, released antigens, and alleviated immunosuppression by blocking IDO1.
- Significant suppression of primary tumors and distant metastases was observed, along with a potent systemic abscopal effect and durable antitumor immunity.
Conclusions:
- The developed multifunctional nanoplatform offers a transformative strategy for precision medicine in TNBC, utilizing NIR-II imaging-guided therapy.
- This approach effectively converts 'cold' tumors into 'hot' ones, eradicating metastatic and immunosuppressive malignancies.
- The integrated strategy shows promise for overcoming treatment resistance and establishing long-term antitumor immunity.
