Converting Lysosomes into Photothermal Organelles Enables Nanoparticle-Free Tumor Ablation via Intracellular Vapor Bubbles

Converting Lysosomes into Photothermal Organelles Enables Nanoparticle-Free Tumor Ablation via Intracellular Vapor Bubbles | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Converting Lysosomes into Photothermal Organelles Enables Nanoparticle-Free Tumor Ablation via Intracellular Vapor Bubbles View ORCID Profile Tao Lu , View ORCID Profile Cristina Muntean , View ORCID Profile Félix Sauvage , View ORCID Profile Deep Punj , View ORCID Profile Herlinde De Keersmaecker , View ORCID Profile Femke Baeke , View ORCID Profile Riet De Rycke , Kelly Lemeire , Philippe Tummers , Weiran Li , Chloë De Clercq , View ORCID Profile Bernd Vanmeerhaeghe , View ORCID Profile Kaat Durinck , View ORCID Profile Olivier De Wever , View ORCID Profile Katrien Remaut , View ORCID Profile Kevin Braeckmans , View ORCID Profile Stefaan C. De Smedt , View ORCID Profile Koen Raemdonck doi: https://doi.org/10.64898/2026.01.23.698471 Tao Lu 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tao Lu Cristina Muntean 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Cristina Muntean Félix Sauvage 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Félix Sauvage Deep Punj 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Deep Punj Herlinde De Keersmaecker 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 3 Ghent Light Microscopy Core, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Herlinde De Keersmaecker Femke Baeke 4 Department of Biomedical Molecular Biology, Ghent University , Ghent, Belgium 5 VIB BioImaging Core, VIB-UGent Center for Inflammation Research , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Femke Baeke Riet De Rycke 4 Department of Biomedical Molecular Biology, Ghent University , Ghent, Belgium 5 VIB BioImaging Core, VIB-UGent Center for Inflammation Research , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Riet De Rycke Kelly Lemeire 4 Department of Biomedical Molecular Biology, Ghent University , Ghent, Belgium 6 HistoCore, VIB-UGent Center for Inflammation Research , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Philippe Tummers 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 7 Department of Gynaecology, Ghent University Hospital , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Weiran Li 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chloë De Clercq 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bernd Vanmeerhaeghe 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Bernd Vanmeerhaeghe Kaat Durinck 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 8 Pediatric Precision Oncology Lab, Department of Biomolecular Medicine, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kaat Durinck Olivier De Wever 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 9 Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Olivier De Wever Katrien Remaut 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Katrien Remaut Kevin Braeckmans 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 3 Ghent Light Microscopy Core, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kevin Braeckmans Stefaan C. De Smedt 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium 3 Ghent Light Microscopy Core, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stefaan C. De Smedt Koen Raemdonck 1 Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium 2 Cancer Research Institute Ghent, Ghent University , Ghent, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Koen Raemdonck For correspondence: Koen.Raemdonck{at}UGent.be Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Photothermal nanomaterials enable precise tumor ablation but face limitations in biodistribution, tissue penetration, toxicity, and biodegradability. Here, we present a unique concept for nanoparticle-free photothermal therapy based on the lysosomal entrapment of cationic amphiphilic small molecular dyes for spatially controlled vapor bubble (VB)-mediated tumor cell ablation. This strategy, which exploits a universal biological and physical effect, employs intracellular pH gradients for extensive local dye enrichment in acidified organelles, transforming them into transient endogenous nanosized photothermal reactors for subsequent light activation. Using sunitinib, a clinically approved lysosomotropic anticancer drug, and the commercially available dye LysoTracker™ Deep Red, lacking intrinsic anticancer activity, we demonstrate pulsed laser-induced VB formation specifically from dye-loaded lysosomes, leading to selective photomechanical disruption of various cancer cell models across 2D cultures, 3D spheroids, patient-derived neuroblastoma tumoroids and tumor fragments from an ovarian carcinoma patient. This approach allows precise, low-fluence and wavelength-tunable cancer tissue ablation without the need for synthetic photoresponsive nanoparticles. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared China Scholarship Council , 202208320061 European Research Council , 101075873 (Project: DYE-LIGHT) European Innovation Council , 101071105 (Project: NOVISTEM) Kom op Tegen Kanker (KOTK) , STI.VLK.2022.0003.01 Villa Joep , STI.DIV.2020.0019.01 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted January 23, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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De Smedt , Koen Raemdonck bioRxiv 2026.01.23.698471; doi: https://doi.org/10.64898/2026.01.23.698471 Share This Article: Copy Citation Tools Converting Lysosomes into Photothermal Organelles Enables Nanoparticle-Free Tumor Ablation via Intracellular Vapor Bubbles Tao Lu , Cristina Muntean , Félix Sauvage , Deep Punj , Herlinde De Keersmaecker , Femke Baeke , Riet De Rycke , Kelly Lemeire , Philippe Tummers , Weiran Li , Chloë De Clercq , Bernd Vanmeerhaeghe , Kaat Durinck , Olivier De Wever , Katrien Remaut , Kevin Braeckmans , Stefaan C. De Smedt , Koen Raemdonck bioRxiv 2026.01.23.698471; doi: https://doi.org/10.64898/2026.01.23.698471 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Bioengineering Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45592) Biophysics (22958) Cancer Biology (20204) Cell Biology (27430) Clinical Trials (138) Developmental Biology (14199) Ecology (21485) Epidemiology (2067) Evolutionary Biology (25889) Genetics (16403) Genomics (23920) Immunology (19115) Microbiology (43383) Molecular Biology (18434) Neuroscience (95525) Paleontology (716) Pathology (3049) Pharmacology and Toxicology (5228) Physiology (8314) Plant Biology (16341) Scientific Communication and Education (2121) Synthetic Biology (4664) Systems Biology (10430) Zoology (2435)

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