Breast cancer remains the most widespread malignancy affecting women globally, representing a critical challenge for modern oncology and medical research. Innovative therapies are urgently needed to improve patient outcomes while minimizing harm to healthy tissues. Among emerging approaches, phototheranostics has attracted significant interest due to its ability to combine diagnosis and treatment through the controlled use of light. This technology leverages light’s unique properties to achieve non-invasive, real-time imaging and simultaneous localized therapy, heralding a new era in precision oncology.
Photothermal therapy (PTT) stands out as a promising modality within phototheranostics. It utilises photothermal agents capable of converting absorbed light energy into heat, thereby inducing localized hyperthermia to ablate cancerous cells. Ideally, these agents should possess tumor-targeting abilities to maximize efficacy and reduce collateral damage. Yet, despite its appeal, PTT faces substantial translational hurdles. The delicate balance between generating sufficient heat to eradicate tumors and avoiding thermal injury to surrounding normal tissue remains challenging, and incomplete tumor ablation risks recurrence and metastasis.
A groundbreaking study published in the Proceedings of the National Academy of Sciences presents a novel dual-laser photothermal therapy (DLPTT) protocol designed to overcome the inherent limitations of conventional PTT. This interdisciplinary effort, led by ZHANG Pengfei at the Shenzhen Institute of Advanced Technology and conducted in collaboration with researchers from Korea University, the University of Texas at Austin, and Nanjing University of Posts and Telecommunications, introduces a two-step laser irradiation strategy that dramatically enhances therapeutic precision and efficacy.
The innovation rests upon the use of near-infrared (NIR) photothermal agents with aggregation-induced emission properties, which enable both superior tumor targeting and advanced imaging capabilities. In this context, the DLPTT method employs two distinct laser wavelengths sequentially, each optimized for specific therapeutic milestones. The initial phase involves a short 808 nm laser exposure lasting two minutes, calibrated to raise tumor temperatures to approximately 50°C. This step induces DNA damage and crucially suppresses the expression of heat shock protein 70 (HSP70), a molecular chaperone known to confer heat resistance to tumor cells.
By dampening HSP70 activity, the DLPTT approach effectively sensitizes cancer cells to subsequent thermal stress, addressing one of the principal biological hurdles that have limited PTT efficacy. The second phase applies a longer treatment with a 1,064 nm laser, extending over 13 minutes with tissue temperatures maintained around 43°C. This carefully controlled heating facilitates the ablation of residual tumor cells while minimizing inflammatory responses that often accompany aggressive thermal therapies. The two-stage process thus exploits the differential biological responses of tumor cells to heat, ensuring enhanced destruction of malignant tissue with reduced side effects.
Critical to the success of this approach is the integration of second near-infrared window (NIR-II) fluorescence imaging combined with photoacoustic imaging. NIR-II imaging benefits from deeper tissue penetration and reduced scattering compared to conventional imaging modalities, allowing for more precise localization of tumors deep within biological tissues. This dual-imaging modality provides dynamic, high signal-to-noise ratio images that guide the targeted laser irradiation, ensuring that therapeutic heat is confined to malignant tissues. In preclinical 4T1 breast cancer mouse models, this dual-imaging strategy demonstrated striking tumor growth inhibition without apparent systemic toxicity.
Comprehensive in vivo biosafety assessments further validated the clinical potential of DLPTT. Mice subjected to treatment exhibited stable body weight trajectories and minimal elevation of inflammatory cytokines, indicators of low systemic toxicity. These findings suggest that DLPTT achieves a high therapeutic index, effectively eradicating tumors while preserving overall physiological homeostasis. Maintaining biosafety is of paramount importance in any translational cancer therapy, and this study sets a precedent for combining effective tumor ablation with a favorable safety profile.
This dual-laser methodology also advances the field of aggregation-induced emission (AIE) materials, which have garnered increasing attention for their unique photophysical properties in biomedical applications. The use of AIE-active photothermal agents allows for enhanced light absorption, efficient heat generation, and superior imaging capacity, making them ideal candidates for integrated phototheranostic platforms. By harnessing these materials, the research team has demonstrated a scalable and versatile approach that could be adapted for a variety of solid tumors beyond breast cancer.
Looking forward, this pioneering work opens multiple avenues for future exploration and clinical translation. Of particular interest is the potential combination of DLPTT with immunotherapy agents, which could synergistically activate systemic anti-tumor immune responses while locally controlling primary tumors. Such integration holds promise for combatting tumor metastasis and recurrence, challenges that conventional therapies struggle to address effectively. The strategic enhancement of tumor ablation through DLPTT may prime the immune system for durable tumor suppression.
Moreover, the dual-laser strategy addresses the Achilles’ heel of traditional PTT by mitigating treatment resistance mechanisms and restricting thermal damage. This fine-tuned control over laser parameters and treatment timing exemplifies the growing sophistication in photomedical engineering. As laser technology continues to advance, future devices may incorporate adaptive feedback systems to further personalize therapy based on real-time imaging and thermal monitoring, pushing the boundaries of precision medicine.
In summary, the study from the Shenzhen Institute of Advanced Technology and collaborators represents a significant step forward in breast cancer phototheranostics. By combining dual-wavelength laser irradiation, cutting-edge NIR-II fluorescence and photoacoustic imaging techniques, and innovative photothermal agents, the DLPTT approach achieves highly effective tumor eradication with minimal side effects in preclinical models. This integrated method promises to transform the therapeutic landscape for breast cancer and sets a new benchmark for photothermal therapeutic strategies.
The implications of this research extend beyond breast cancer, suggesting a versatile platform adaptable to other malignancies requiring precise ablation. The successful clinical translation of DLPTT depends on further validation in larger animal models and eventual human trials, but the foundation laid by these findings is robust and inspiring. As research continues to optimize material properties, laser systems, and combinational therapies, phototheranostics may emerge as a cornerstone treatment modality in the era of personalized oncology.
Ultimately, this dual-laser photothermal therapy highlights the power of interdisciplinary collaboration across materials science, bioengineering, and clinical oncology. By merging fundamental scientific insights with practical therapeutic innovations, this study embodies the promise of next-generation cancer care—offering hope for more effective, safer, and less invasive treatment options that can significantly improve patient quality of life worldwide.
Subject of Research: Breast cancer phototheranostics, dual-laser photothermal therapy, aggregation-induced emission materials, near-infrared imaging.
Article Title: Dual-laser “808 and 1,064 nm” strategy that circumvents the Achilles’ heel of photothermal therapy
News Publication Date: 9-Jun-2025
Web References:
https://doi.org/10.1073/pnas.2503574122
References: Proceedings of the National Academy of Sciences, 2025.
Keywords: Breast cancer, photothermal therapy, dual-laser strategy, near-infrared imaging, aggregation-induced emission, tumor ablation, molecular heat shock protein suppression, phototheranostics, NIR-II fluorescence, photoacoustic imaging.
