Achieving precise tumor ablation without damaging surrounding healthy tissue remains a significant challenge in cancer therapy,particularly for deep-seated or irregularly shaped tumors.Traditional laser-based approach...Achieving precise tumor ablation without damaging surrounding healthy tissue remains a significant challenge in cancer therapy,particularly for deep-seated or irregularly shaped tumors.Traditional laser-based approaches,although minimally invasive,are often limited by insufficient tissue penetration,uncontrolled thermal damage,and narrow therapeutic windows.We introduce GHz high-repetition-rate pulsed lasers as a transformative modality for tumor ablation.This approach capitalizes on the thermal accumulation effect of GHz pulse trains,in which the pulse interval is significantly shorter than the thermal relaxation time of biological tissue.Such a regime enables efficient and localized heat deposition in tumor regions.By precisely tuning the repetition frequency,pulse duration,and energy density,we establish a dynamic“ablation-cooling”cycle:rapid energy delivery followed by transient inter-pulse cooling.This thermal modulation ensures sharply confined ablation zones with reduced collateral damage.Our systematic investigation of laser-tissue interaction parameters demonstrates that GHz lasers offer superior spatial selectivity,minimized off-target injury,and enhanced treatment safety,presenting a compelling rationale for clinical translation of this paradigm in precision photothermal oncology.展开更多
Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade,which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles.Ho...Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade,which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles.However,the optothermal temperature field was merely employed for in-situ manipulation of nanoparticles,its potential for identifying bio-nanoparticles remains largely untapped.Hence,based on the synergistic effect of optothermal manipulation and CRIPSR-based bio-detection,we developed CRISPR-powered optothermal nanotweezers(CRONT).Specifically,by harnessing diffusiophoresis and thermo-osmotic flows near the substrate upon optothermal excitation,we successfully trapped and enriched DNA functionalized gold nanoparticles,CRISPR-associated proteins,as well as DNA strands.Remarkably,we built an optothermal scheme for enhancing CRISPR-based single-nucleotide polymorphism(SNP)detection at single molecule level,while also introducing a novel CRISPR methodology for observing nucleotide cleavage.Therefore,this innovative approach has endowed optical tweezers with DNA identification ability in aqueous solution which was unattainable before.With its high specificity and feasibility for in-situ bio-nanoparticle manipulation and identification,CRONT will become a universal tool in point-of-care diagnosis,biophotonics,and bio-nanotechnology.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3207204)the National Natural Science Foundation of China(Grant No.52293422)+6 种基金the Basic and Applied Basic Research Foundation of Guangdong Province-Regional Joint Fund-Key Projects(Grant Nos.2022B1515120012 and 2023B0101200003)the Department of Science and Technology of Guangdong Province(Grant No.2023B0101200003)the Science and Technology Innovation Commission of Shenzhen(Grant Nos.JCYJ20240813141317023,KJZD20240903095707010,KCXFZ20230731093259009,JCYJ20220818102618040,GJHZ20220913143207014,JCYJ20241202130558075,and KJZD20230923114002005)the Shenzhen Medical Research Fund(Grant Nos.D2301014 and D2402002)the Chemical Department of Hangzhou Normal University and the Ministry of Education Key Laboratory Open Scientific Projects Fund(Grant No.KFJJ2023007)the Medical-Engineering Interdisciplinary Research Foundation of Shenzhen University,the Research Team Cultivation Program of Shenzhen University(Grant No.2023QNT008)the Graduate Independent Innovation Achievement Cultivation Project of Shenzhen University in 2025(Grant No.315-000066010715).
文摘Achieving precise tumor ablation without damaging surrounding healthy tissue remains a significant challenge in cancer therapy,particularly for deep-seated or irregularly shaped tumors.Traditional laser-based approaches,although minimally invasive,are often limited by insufficient tissue penetration,uncontrolled thermal damage,and narrow therapeutic windows.We introduce GHz high-repetition-rate pulsed lasers as a transformative modality for tumor ablation.This approach capitalizes on the thermal accumulation effect of GHz pulse trains,in which the pulse interval is significantly shorter than the thermal relaxation time of biological tissue.Such a regime enables efficient and localized heat deposition in tumor regions.By precisely tuning the repetition frequency,pulse duration,and energy density,we establish a dynamic“ablation-cooling”cycle:rapid energy delivery followed by transient inter-pulse cooling.This thermal modulation ensures sharply confined ablation zones with reduced collateral damage.Our systematic investigation of laser-tissue interaction parameters demonstrates that GHz lasers offer superior spatial selectivity,minimized off-target injury,and enhanced treatment safety,presenting a compelling rationale for clinical translation of this paradigm in precision photothermal oncology.
基金supported by the National Natural Science Foundation of China(62275164,61905145,62275168,61775148)National Key Research and Development Program of China(No.2022YFA1206300)+8 种基金Guangdong Natural Science Foundation and Province Project(2021A1515011916,2023A1515012250)Foundation from Department of Science and Technology of Guangdong Province(2021QN02Y124)Shenzhen Science and Technology R&D and Innovation Foundation(JCYJ20200109105608771)Shenzhen Key Laboratory of Photonics and Biophotonics(ZDSYS20210623092006020)The Research Grants Council(RGC)of Hong Kong China(RGC14207920)Innovation Team Project of Department of Education of Guangdong Province(2018KCXTD026)Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah(KEP-MSc-70-130-42)King Khalid University through Research Center for Advanced Materials Science(RCAMS)(RCAMS/KKU/006/21)Medical-Engineering Interdisciplinary Research Foundation of Shenzhen University。
文摘Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade,which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles.However,the optothermal temperature field was merely employed for in-situ manipulation of nanoparticles,its potential for identifying bio-nanoparticles remains largely untapped.Hence,based on the synergistic effect of optothermal manipulation and CRIPSR-based bio-detection,we developed CRISPR-powered optothermal nanotweezers(CRONT).Specifically,by harnessing diffusiophoresis and thermo-osmotic flows near the substrate upon optothermal excitation,we successfully trapped and enriched DNA functionalized gold nanoparticles,CRISPR-associated proteins,as well as DNA strands.Remarkably,we built an optothermal scheme for enhancing CRISPR-based single-nucleotide polymorphism(SNP)detection at single molecule level,while also introducing a novel CRISPR methodology for observing nucleotide cleavage.Therefore,this innovative approach has endowed optical tweezers with DNA identification ability in aqueous solution which was unattainable before.With its high specificity and feasibility for in-situ bio-nanoparticle manipulation and identification,CRONT will become a universal tool in point-of-care diagnosis,biophotonics,and bio-nanotechnology.