Conventional ablation therapies, which include the application of heat, chemical agents, or non-specific laser wavelengths, often struggle to discriminate between cancerous and normal pancreatic tissue. This lack of precision frequently leads to collateral damage, exacerbating post-operative complications and impairing organ function. Recognizing these limitations, Liang’s group sought a novel strategy that capitalizes on tumor-specific molecular characteristics to improve accuracy and safety. By identifying a laser wavelength precisely tuned to the collagen absorption peak within PDAC tumors, they developed a femtosecond mid-infrared laser system capable of selectively targeting the malignancy.

Central to this innovation is the utilization of a 6.1-micron wavelength laser, which aligns closely with the vibrational absorption bands of collagen fibers. Collagen is markedly overexpressed in PDAC tumor stroma compared to healthy pancreatic tissue, making it an ideal endogenous biomarker for selective targeting. Employing femtosecond pulses—ultrafast bursts of laser energy—maximizes the ablation effect while minimizing thermal diffusion, thereby preserving adjacent non-cancerous structures. This molecular resonance strategy, distinct from conventional photothermal ablation, leverages the intrinsic biochemical disparity between tumor and normal tissue to effect precise surgical intervention.

The team collaborated with experts from Nanyang Technological University to enhance clinical deliverability by incorporating an anti-resonant hollow-core fiber with an outer diameter under 400 microns. This cutting-edge fiber optic cable ensures efficient transmission of the mid-infrared laser light into the human body, with bending losses maintained below 1 dB/m even at clinically relevant curvature radii. Engineered for durability with biocompatible polyimide jackets and sapphire endcaps, the fiber facilitates minimally invasive access deep within the pancreatic region, overcoming major practical barriers to deploying mid-infrared laser therapy in vivo.

Extensive ex vivo experimentation on tumor samples obtained from 13 patients demonstrated that this wavelength-selective ablation method outperforms traditional non-resonant wavelengths, such as 1 or 3 microns, by two to three times in tumor destruction efficiency. Histological analyses confirmed substantial tumor eradication accompanied by remarkable preservation of normal pancreatic parenchyma. These findings suggest a substantial leap forward toward reducing the morbidity associated with standard surgical or thermal ablation approaches, which frequently compromise organ function and patient quality of life.

This technology’s clinical promise extends beyond improved efficacy; it holds the potential to fundamentally change the therapeutic landscape of pancreatic cancer by enabling safer, less invasive tumor resections. By sparing healthy tissue, this laser system could significantly curtail the risk of complications such as pancreatic fistula, infection, and exocrine or endocrine insufficiency. Moreover, its adaptability offers physicians a powerful tool to tailor treatments individually based on tumor molecular composition, marking a pioneering stride toward precision oncology modalities that extend well past current standards.

Future work aims to refine laser parameters and fiber configuration to optimize ablation depth, uniformity, and stability during clinical procedures. Integration with optical coherence tomography is underway to enable real-time imaging-guided tumor margin delineation and immediate therapeutic feedback. This combined diagnostic-therapeutic platform aspires to perform simultaneous cancer detection and ablation, potentially supporting intraoperative decision-making with unprecedented accuracy.

Beyond pancreatic cancer, this molecular resonance laser strategy could be adapted for other malignancies characterized by distinctive extracellular matrix compositions or molecular aberrations. Tumors rich in specific biomolecules might become amenable to similarly selective ablation, opening a new frontier in laser oncology where treatment specificity is dictated by intrinsic tissue biochemistry rather than extrinsic energy delivery parameters alone. Such an approach could fundamentally shift laser-assisted cancer therapy paradigms across diverse tumor types and anatomical locations.

Despite its profound potential, translation into clinical practice will require meticulous biological safety evaluations and rigorous clinical trials to establish long-term safety profiles, optimal dosing, and efficacy benchmarks. The research team emphasizes the need for structured studies that assess risks alongside therapeutic benefits to pave the way for regulatory approvals and widespread adoption. Refinement of the integrated laser and fiber delivery system also remains a priority to ensure ease of use, patient safety, and procedural reliability in operating rooms and endoscopy suites.

This pioneering research, published in the high-impact optics journal Optica, underscores the transformative role of photonics in modern medicine. By harnessing the specificity of molecular absorption signatures, this laser ablation technology exemplifies how interdisciplinary innovation at the junction of optics, engineering, and oncology can yield tangible clinical breakthroughs. As the relentless quest to tame pancreatic cancer continues, such advances bring hope for more effective, less invasive therapies that preserve life and improve outcomes for patients worldwide.

Selective tumor ablation using femtosecond mid-infrared lasers resonant with collagen represents a paradigm shift in targeted cancer therapy, emphasizing molecular fingerprinting to navigate the complexity of tumor biology. This work not only advances the state of the art in pancreatic cancer treatment but also sets a precedent for leveraging molecular resonances for precision tissue ablation in the future. By reducing collateral damage and enhancing treatment selectivity, it opens a promising path toward safer, minimally invasive surgical options that ultimately may save countless lives.

Subject of Research: Pancreatic ductal adenocarcinoma (PDAC) selective ablation using femtosecond mid-infrared laser technology targeting collagen molecular absorption.

Article Title: Selective tumor ablation via femtosecond laser resonant with collagen.

Web References:

• Optica Journal: https://opg.optica.org/optica/abstract.cfm?doi=10.1364/OPTICA.561337
• Sichuan University: https://en.scu.edu.cn/
• Nanyang Technological University: https://www.ntu.edu.sg/

References:
D. Zhang, X. Huang, X. Yang, N. Xia, K. Tian, J. Guo, M. Xiang, L. He, Z. Fu, A. Deng, H. Wu, Y. Wang, W. Chang, B. Tian, J. Xiong, Q. Wang, A. Gomes, H. Liang, “Selective tumor ablation via femtosecond laser resonant with collagen,” Optica, vol. 12, pp. 1578-1586, 2025. DOI: 10.1364/OPTICA.561337.

Image Credits: Houkun Liang, Sichuan University.

Keywords: Cancer research, pancreatic cancer, tumor ablation, femtosecond laser, mid-infrared laser, collagen targeting, selective tissue ablation, minimally invasive surgery, photonics in medicine, laser oncology, molecular fingerprinting, optical fiber delivery.

Among phototheranostic techniques, photothermal therapy (PTT) stands out as a promising modality. PTT utilizes photothermal agents capable of absorbing specific wavelengths of light and converting them efficiently into heat, thereby raising temperatures locally to induce tumor cell death. A critical aspect of this approach lies in the tumor-targeting ability of photothermal agents, which allows selective ablation of malignant tissue while sparing normal cells. However, widespread clinical adoption of PTT has been hampered by several obstacles, chief among them the risk of overheating, which can cause collateral damage to surrounding healthy tissues, and the sometimes insufficient tumor eradication leading to relapse.

Addressing these challenges, a recent collaborative research effort led by Professor ZHANG Pengfei of the Shenzhen Institute of Advanced Technology (SIAT) and his international colleagues has introduced an innovative dual-laser photothermal therapy (DLPTT) strategy. Their work, published in the prestigious journal Proceedings of the National Academy of Sciences, pioneers the use of two wavelengths—808 nm and 1,064 nm—in a sequential treatment protocol designed to enhance tumor ablation while reducing adverse effects. This breakthrough leverages specially engineered near-infrared photothermal agents exhibiting aggregation-induced emission (AIE) properties, which bolster imaging clarity and photothermal conversion efficiency.

The DLPTT strategy unfolds in two carefully calibrated stages. Initially, the tumor site undergoes a brief, high-temperature exposure using an 808 nm laser for approximately two minutes, achieving local temperatures around 50 °C. This phase achieves a crucial biological effect: it induces DNA damage in tumor cells and suppresses the expression of heat shock protein 70 (HSP70), a molecular chaperone known to confer thermotolerance. By inhibiting HSP70, this step effectively dismantles a key cellular defense mechanism, rendering cancer cells more vulnerable to subsequent treatment.

Following this priming stage, the therapy transitions to a longer-duration 1,064 nm laser irradiation, maintained at a slightly lower temperature near 43 °C over 13 minutes. This gentler heating phase is optimized to ablate residual tumor cells without provoking excessive inflammation or thermal injury to adjacent healthy tissues. The sequential use of two laser wavelengths capitalizes on their distinct tissue penetration depths and absorption profiles, enabling precise modulation of the tumor microenvironment and maximizing treatment efficacy.

A hallmark of this DLPTT protocol is the integration of second near-infrared window (NIR-II) fluorescence imaging, combined with photoacoustic imaging techniques. NIR-II imaging offers profound advantages, including deeper tissue penetration and significantly reduced scattering, which together produce images with enhanced signal-to-noise ratios. This highly sensitive imaging modality facilitates real-time visualization of tumors, even in deep tissue contexts, allowing clinicians to accurately localize and monitor the response of malignant lesions throughout therapy. Photoacoustic imaging complements this by providing additional anatomical and functional information, enriching the precision of treatment guidance.

Preclinical validation of this approach was conducted using the 4T1 breast cancer mouse model, a well-established system that closely mimics aggressive human breast cancer behavior. The results demonstrated that DLPTT significantly suppressed tumor growth, outstripping conventional single-laser PTT approaches in both effectiveness and safety. Importantly, treated animals showed no marked side effects, with stable body weights and no evident toxicity, underscoring the biosafety profile of this dual-laser regimen.

Further in vivo studies confirmed that DLPTT minimized systemic inflammatory responses, a common complication in thermal therapies. The reduction in inflammatory cytokine production suggests that the dual-laser strategy not only eradicates cancer cells but also preserves normal tissue homeostasis, which is vital for preventing adverse immune reactions and facilitating patient recovery.

Beyond its immediate therapeutic impact, this research also marks a significant advancement in the development of aggregation-induced emission (AIE) materials. AIE luminogens are a novel class of compounds whose fluorescence intensities increase upon aggregation, contrasting with conventional fluorophores that often suffer from quenching. Their use in photothermal agents enhances both imaging clarity and therapeutic precision, positioning them as versatile tools in the expanding field of phototheranostics.

Looking forward, the authors envision a promising future where DLPTT is integrated synergistically with immunotherapy. The combination of precise tumor ablation and immune system modulation could provide a powerful strategy to combat cancer metastasis and recurrence, addressing two of the most daunting challenges in oncology. By dismantling tumor cells locally and simultaneously activating systemic antitumor immunity, such combinatorial therapies hold the potential to redefine cancer care.

This groundbreaking study exemplifies the transformative potential of light-based technologies in modern medicine. By refining photothermal therapy through innovative laser strategies and advanced imaging, it paves the way for minimally invasive, highly effective cancer treatments that prioritize patient safety without compromising therapeutic potency. As research continues to evolve, phototheranostics promises to become a cornerstone of personalized oncology, offering hope for millions affected by breast cancer worldwide.

Subject of Research: Breast cancer photothermal therapy using dual-laser strategy and aggregation-induced emission materials

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

Keywords: Breast cancer, Photothermal therapy, Dual-laser strategy, Near-infrared imaging, Aggregation-induced emission, Phototheranostics, NIR-II fluorescence, Photoacoustic imaging, Tumor ablation, Heat shock protein, Immunotherapy integration