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Published on: August 23, 2024
Enzyme-Activatable and Tumor-Targeted Nanosystem for Real-Time Imaging and Synergistic Zn2+-Interference Photothermal
Yujia Zhang1, Chen Zhao1, Jukun Yang1
1College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China.
Abstract:
Bone metastasis is a frequent and debilitating complication in advanced breast cancer. Monitoring and treating bone metastasis remains challenging due to the inability of current imaging modalities to capture early molecular changes or provide real-time therapeutic feedback. Here, we report a multifunctional nanosensor (APAZPs) with matrix metalloproteinase-2 (MMP-2)-activatable fluorescence imaging, Zn2+ interference, and photothermal therapy capabilities, for the detection of metastatic lesions. To our knowledge, this is the first nanosystem that combines MMP-2-activatable imaging with Zn2+ interference and photothermal therapy for real-time management of breast cancer bone metastasis. The nanosystem was constructed by assembling gold nanotriangles functionalized with an MMP-2-cleavable Cy5 peptide and the tumor-targeting aptamer AS1411, with PDA-coated AA-[Zn(OH)4]2- nanoparticles via NH2-PEG-SH linkers. The fluorescence of Cy5 in the sensor is restored upon MMP-2-mediated cleavage of the peptide. The sensor exhibited high specificity and a low detection limit of 0.107 ng/mL. In the acidic tumor microenvironment, Zn2+ release is triggered, and the PDA shell generates near-infrared (NIR) photothermal heating with a conversion efficiency of 50.93%. These coordinated responses induced apoptosis in vitro, markedly inhibited cell migration and invasion, and achieved deep penetration into three-dimensional tumor spheroids. In vivo experiments showed that APAZPs preferentially accumulated at bone metastatic sites, and upon 808 nm irradiation, they significantly suppressed tumor growth and reduced tumor volume to 45% of the initial size without observable systemic toxicity. This activatable nanosystem is a versatile platform for real-time imaging and synergistic therapy. It is a promising tool for precision intervention in breast cancer bone metastasis.
Insights
A new nanosensor detects breast cancer bone metastasis using MMP-2-activatable imaging and photothermal therapy. This system offers real-time monitoring and treatment for improved patient outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Bone metastasis is a significant challenge in advanced breast cancer, with current imaging lacking early detection and real-time therapeutic feedback.
- Existing methods struggle to monitor the molecular changes associated with metastatic lesions and guide treatment effectively.
Purpose of the Study:
- To develop a multifunctional nanosensor (APAZPs) for early detection and synergistic therapy of breast cancer bone metastasis.
- To combine MMP-2-activatable fluorescence imaging, Zn2+ interference, and photothermal therapy into a single platform for real-time management.
Main Methods:
- ASSEMBLY: Gold nanotriangles functionalized with MMP-2-cleavable peptide and AS1411 aptamer were assembled with PDA-coated AA-[Zn(OH)4]2- nanoparticles.
- ACTIVATION: Fluorescence restored upon MMP-2 cleavage; Zn2+ release triggered in acidic tumor microenvironment; PDA shell enabled NIR photothermal heating.
- ASSESSMENT: Evaluated specificity, detection limit, in vitro apoptosis/migration inhibition, 3D spheroid penetration, and in vivo tumor suppression.
Main Results:
- The nanosensor demonstrated high specificity and a low detection limit (0.107 ng/mL) for metastatic lesions.
- The system induced apoptosis, inhibited cell migration/invasion in vitro, and penetrated 3D tumor spheroids.
- In vivo, APAZPs accumulated at bone metastatic sites, significantly suppressed tumor growth (45% reduction), with no observable toxicity.
Conclusions:
- The developed activatable nanosystem (APAZPs) is a versatile platform for real-time imaging and synergistic therapy of breast cancer bone metastasis.
- This technology shows promise for precision intervention, offering improved monitoring and therapeutic feedback.
- The combination of MMP-2-activatable imaging, Zn2+ interference, and photothermal therapy represents a novel approach for managing bone metastases.
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