Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Cancer metastasis remains a significant challenge in treatment.
• Nanoparticle-mediated photothermal therapy (PTT) offers a promising approach.
• Current PTT agents often lack specificity and can cause side effects like metastasis.

Purpose of the Study:

• To investigate the modulation of cancer metastasis by tuning photothermal temperature during PTT.
• To develop and characterize a theranostic nanosystem for image-guided PTT.
• To evaluate the impact of different PTT temperatures on tumor eradication and metastasis.

Main Methods:

• Design and characterization of matrix metalloproteinase (MMP)-triggered gold nanodandelions (GNDs@gelatin) for PTT.
• In vitro and in vivo analyses of GNDs@gelatin for theranostic effects and tumor ablation.
• Photoacoustic (PA) imaging for precise PTT planning and MMP activity quantification.
• Transcriptome-based gene profiling (microarray, GO, KEGG) to analyze molecular changes.

Main Results:

• GNDs@gelatin demonstrated specific activation by tumor microenvironment factors (MMP-2/-9 activity and acidity).
• Quantitative PA imaging enabled precise PTT planning and noninvasive MMP activity monitoring.
• Moderate PTT temperatures (43°C < T < 50°C) effectively inhibited metastasis, whereas higher temperatures (>55°C) induced it.
• Gene profiling revealed distinct molecular pathways (e.g., cell migration, proliferation) affected by different PTT temperatures.

Conclusions:

• Judicious tuning of photothermal temperature is critical for controlling cancer metastasis during PTT.
• The developed GNDs@gelatin theranostic nanosystem offers targeted activation, precise imaging, and efficient tumor ablation.
• A 'moderate-is-better' PTT strategy maximizes therapeutic benefits and minimizes metastasis, showing translational potential.