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Updated: Jul 22, 2025
Plasmonic Photothermal Cancer Therapy: Nanoparticle-embedded Tumor-tissue-mimicking Phantoms for Visualizing Photothermal Temperature Distribution
Published on: May 9, 2025
Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics
Mengxin Wang1, Xue Zhang1, Qian Chang1
1Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, International Joint Laboratory of Resource Chemistry, Shanghai Normal University, Shanghai 200234, China.
Abstract:
The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000 nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.
Insights
A new strategy uses tumor microenvironment-activated gold self-assembly to switch from near-infrared-I to NIR-II imaging. This improves deep tumor diagnosis accuracy and enables targeted photothermal therapy, overcoming current limitations.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Photothermal agents for tumor theranostics face challenges with limited penetration depth and damage to healthy tissues.
- Existing near-infrared-I (NIR-I) agents are always 'on,' leading to diagnostic inaccuracies and indiscriminate treatment.
Purpose of the Study:
- To develop a tumor microenvironment (TME)-activated strategy for switching photothermal agents from NIR-I to NIR-II regions.
- To enhance deep-tumor diagnosis accuracy and enable selective photothermal therapy by utilizing TME-mediated gold self-assembly.
Main Methods:
- Utilized zeolitic imidazolate framework-8 (ZIF-8) coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent.
- Investigated the signal transformation from NIR-I to NIR-II upon ZIF-8 dissociation in the TME.
- Evaluated the efficacy of TME-activated NIR-II photothermal therapy in inhibiting tumor growth.
Main Results:
- In normal tissue, only NIR-I photoacoustic imaging signals were detected due to ZIF-8 preventing AuNR aggregation.
- In the TME, ZIF-8 dissociation led to AuNR aggregation, activating NIR-II imaging and attenuating NIR-I signals for accurate tumor visualization.
- TME-activated NIR-II photothermal therapy demonstrated significant tumor growth inhibition.
Conclusions:
- The developed TME-activated NIR-I-to-NIR-II switching strategy enhances deep-tumor diagnosis accuracy.
- This approach minimizes damage to normal tissues by enabling selective photothermal therapy.
- This work presents a novel strategy for creating TME-activated NIR-II smart photothermal agents for improved tumor theranostics.
