17 Jun 2025
SIAT project enhances desired tumor ablation while minimizing damage to healthy tissues.
Photothermal therapy (PTT), in which suitable photosensitive agents or nanoparticles are introduced to malignant tissues and then heated by an incident laser, is a valuable tool in clinical treatment of cancers.The challenge with PTT is always to generate enough localized heat to ablate or destroy those tissues being targeted, but leave surrounding healthy material undamaged.
"This pioneering PTT approach is gaining traction in clinical settings; however, traditional PTT faces inherent limitations," noted a project led by China's Shenzhen Institutes of Advanced Technology (SIAT), which has developed a possible solution.
Described in PNAS, the group demonstrated a new strategy based around dual-wavelength irradiation, which could "revolutionize breast cancer PTT," according to the team.
The dual-laser PTT (DLPTT) method exploits the infra-red absorption properties of the organic molecule termed PM331, already studied as a candidate material for PTT procedures, and whose aggregation-induced thermal behavior is known.
The SIAT project used Pluronic F-127, a commercial copolymer, as the basis for particles within which photosensitive molecules of PM331 could be incorporated in controlled quantities, creating combined "PM331@F127" nanoparticles.
Careful control of the fabrication creates PM331@F127 particles showing good thermal conversion efficiencies of 40 percent and 66 percent at two different excitation wavelengths, 808 and 1,064 nanometers respectively, along with good absorption in the second near-infrared window at longer wavelengths.
"Leveraging these characteristics, we developed a dual-laser PTT strategy that integrates the benefits of traditional high-temperature and low-temperature PTT," noted the SIAT project.
Integration with immunotherapy for clinical care
The project's dual-laser PTT treatment regime takes place in two stages. In the first stage, a short two-minute 808-nanometer laser irradiation induces DNA damage in the adjacent tissues at a temperature of approximately 50 degrees centigrade, while suppressing the response of HSP70, a heat shock protein normally triggered into expression by this kind of thermal damage.
The second stage is an longer treatment with the 1,064 nanometer laser, lasting 13 minutes at around 43 degrees centigrade, which effectively ablates residual cancer cells with minimal inflammatory response.
Tracking the nanoparticles' position and targeting the incident laser was carried out by exploiting the second near-IR absorption of the PM331@F127 particles, along with photoacoustic imaging. Highly precise targeting can be achieved in this way, as well as giving researchers a clearer location of a tumor in deeper tissue, according to the project.
Trials on mice confirmed that DLPTT effectively eradicated tumors while maintaining low toxicity, as evidenced by stable body weights and minimal production of inflammatory cytokines, normally produced in response by the immune system.
"This study promotes the development of imaging-guided tumor phototherapy and extends research frontiers in aggregation-induced emission materials," commented the SIAT group. "Future integration with immunotherapy will potentially provide a powerful means of addressing tumor metastasis and recurrence."
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