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Intratumoral Bacterial-Targeted Cascade-Responsive Sonoafterglow Nanoprobes for Immune Reprogramming and
Yanping Jiang1, Jiawei Zhang1, Jingjing Ye1
1Institute of Functional Nano & Soft Materials & Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou 215123, China.
Analytical Chemistry
|July 12, 2025
Summary
New nanoprobes target bacteria in glioblastoma (GBM) and reprogram the immune system. Ultrasound activates these probes to eliminate tumors, enhance imaging, and overcome blood-brain barrier challenges for effective GBM therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glioblastoma (GBM) is often associated with bacteria that promote tumor growth and immune suppression.
- Current GBM treatments struggle with poor blood-brain barrier (BBB) penetration and overcoming immunosuppressive tumor microenvironments.
- Targeting bacteria and reprogramming tumor-associated macrophages are critical for effective GBM therapy.
Purpose of the Study:
- To develop novel cascade-responsive sonoafterglow nanoprobes for bacteria-targeting, immune reprogramming, and imaging in glioblastoma.
- To enhance GBM treatment by overcoming BBB penetration limitations and modulating the immunosuppressive tumor microenvironment.
- To create a theranostic platform integrating bacterial eradication, tumor cell ablation, and real-time immune monitoring.
Main Methods:
- Development of nanoprobes incorporating a sonoafterglow pro-substrate, sonosensitizer, and maltodextrin for bacterial targeting via the ATP-binding cassette sugar transporter pathway.
- Utilizing ultrasound (US)-induced BBB opening to enhance nanoprobe delivery and accumulation in GBM.
- Investigating the cascade-responsive activation of nanoprobes upon US exposure to generate singlet oxygen (¹O₂) and peroxynitrite (ONOO⁻) for therapeutic effects and imaging.
Main Results:
- Nanoprobes demonstrated selective bacterial targeting and a 1.5-fold increase in GBM accumulation after US-induced BBB opening.
- US activation led to bacteria eradication, tumor cell ablation, and reprogramming of macrophages to a pro-inflammatory phenotype.
- The system enabled precise afterglow activation via ¹O₂ and ONOO⁻ interactions, facilitating real-time imaging of the tumor immune microenvironment.
Conclusions:
- The developed cascade-responsive sonoafterglow nanoprobes offer a promising integrated approach for glioblastoma therapy.
- This platform effectively targets bacteria, modulates the immune microenvironment, and provides real-time imaging capabilities.
- The strategy overcomes key challenges in GBM treatment, including BBB penetration and immunosuppression, paving the way for advanced theranostic applications.
