{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:44:26Z","timestamp":1790117066463,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI R01","award":["5R01CA243164"],"award-info":[{"award-number":["5R01CA243164"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin\u2212phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects for the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe\u2019s effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer that involve optimizing chemotherapy administration for precision and control.<\/jats:p>","DOI":"10.3390\/ijms26031212","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T11:08:23Z","timestamp":1738235303000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fluence Rate-Dependent Kinetics of Light-Triggered Liposomal Doxorubicin Assessed by Quantitative Fluorescence-Based Endoscopic Probe"],"prefix":"10.3390","volume":"26","author":[{"given":"Daniel J.","family":"Rohrbach","sequence":"first","affiliation":[{"name":"Agilent Technologies, Winooski, Vermont, VT 05404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"Aygun-Sunar","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-884X","authenticated-orcid":false,"given":"Jonathan F.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-7522","authenticated-orcid":false,"given":"Ulas","family":"Sunar","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kress, J., Rohrbach, D.J., Carter, K.A., Luo, D., Poon, C., Aygun-Sunar, S., Shao, S., Lele, S., Lovell, J.F., and Sunar, U. (2017). A dual-channel endoscope for quantitative imaging, monitoring, and triggering of doxorubicin release from liposomes in living mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15790-y"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.msec.2014.06.002","article-title":"Current treatment options and drug delivery systems as potential therapeutic agents for ovarian cancer: A review","volume":"45","author":"Ye","year":"2014","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1021\/nn400334y","article-title":"Single-Step Assembly of DOX\/ICG Loaded Lipid\u2013Polymer Nanoparticles for Highly Effective Chemo-photothermal Combination Therapy","volume":"7","author":"Zheng","year":"2013","journal-title":"ACS Nano"},{"key":"ref_4","first-page":"6950","article-title":"Efficacy of liposomes and hyperthermia in a human tumor xenograft model: Importance of triggered drug release","volume":"60","author":"Kong","year":"2000","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jconrel.2019.01.030","article-title":"Pharmacokinetics and pharmacodynamics of liposomal chemophototherapy with short drug-light intervals","volume":"297","author":"Luo","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1158\/1535-7163.MCT-17-0276","article-title":"Vessel-Targeted Chemophototherapy with Cationic Porphyrin-Phospholipid Liposomes","volume":"16","author":"Luo","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1038\/ncomms4546","article-title":"Porphyrin-phospholipid liposomes permeabilized by near-infrared light","volume":"5","author":"Carter","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.jconrel.2015.11.011","article-title":"Porphyrin-phospholipid liposomes with tunable leakiness","volume":"220","author":"Luo","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jconrel.2009.10.034","article-title":"Non-invasive monitoring of intra-tumor drug concentration and therapeutic response using optical spectroscopy","volume":"142","author":"Palmer","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.biomaterials.2015.10.027","article-title":"Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release","volume":"75","author":"Luo","year":"2016","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1002\/smll.201503966","article-title":"Rapid Light-Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin\u2013Phospholipids","volume":"12","author":"Luo","year":"2016","journal-title":"Small"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.7150\/thno.15701","article-title":"Sphingomyelin Liposomes Containing Porphyrin-phospholipid for Irinotecan Chemophototherapy","volume":"6","author":"Carter","year":"2016","journal-title":"Theranostics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/acs.molpharmaceut.5b00653","article-title":"Metal Chelation Modulates Phototherapeutic Properties of Mitoxantrone-Loaded Porphyrin\u2013Phospholipid Liposomes","volume":"13","author":"Carter","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nchem.2236","article-title":"Functionalization of cobalt porphyrin\u2013phospholipid bilayers with his-tagged ligands and antigens","volume":"7","author":"Shao","year":"2015","journal-title":"Nat. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/sj.bjc.6690361","article-title":"Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light","volume":"80","author":"Pogue","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.acra.2013.11.013","article-title":"Preoperative Mapping of Nonmelanoma Skin Cancer Using Spatial Frequency Domain and Ultrasound Imaging","volume":"21","author":"Rohrbach","year":"2014","journal-title":"Acad. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1021\/nn305011p","article-title":"Markedly Enhanced Permeability and Retention Effects Induced by Photo-immunotherapy of Tumors","volume":"7","author":"Sano","year":"2012","journal-title":"ACS Nano"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.pdpdt.2017.10.005","article-title":"Assessing daylight & low-light photodynamic therapy efficacy, using biomarkers of photophysical, biochemical and biological damage metrics in situ","volume":"20","author":"LaRochelle","year":"2017","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1364\/BOE.4.000531","article-title":"Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging","volume":"4","author":"Sunar","year":"2013","journal-title":"Biomed. Opt. Express"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1097\/DSS.0000000000000183","article-title":"A Prospective Study of Pain Control by a 2-Step Irradiance Schedule During Topical Photodynamic Therapy of Nonmelanoma Skin Cancer","volume":"40","author":"Zeitouni","year":"2014","journal-title":"Dermatol. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.7150\/thno.16183","article-title":"Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy","volume":"6","author":"Mallidi","year":"2016","journal-title":"Theranostics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"469","DOI":"10.7150\/thno.10694","article-title":"Nano-Enabled SERS Reporting Photosensitizers","volume":"5","author":"Farhadi","year":"2015","journal-title":"Theranostics"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mo, W., Rohrbach, D., and Sunar, U. (2012). Imaging a photodynamic therapy photosensitizer in vivo with a time-gated fluorescence tomography system. J. Biomed. Opt., 17.","DOI":"10.1117\/1.JBO.17.7.071306"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.acra.2013.11.009","article-title":"Mesoscopic Fluorescence Tomography of a Photosensitizer (HPPH) 3D Biodistribution in Skin Cancer","volume":"21","author":"Ozturk","year":"2014","journal-title":"Acad. Radiol."},{"key":"ref_25","first-page":"130","article-title":"Assessment of the specificity of a new folate-targeted photosensitizer for peritoneal metastasis of epithelial ovarian cancer to enable intraperitoneal photodynamic therapy. A preclinical study","volume":"13","author":"Schmitt","year":"2015","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1364\/AO.36.007257","article-title":"Absorbed photodynamic dose from pulsed versus continuous wave light examined with tissue-simulating dosimeters","volume":"36","author":"Pogue","year":"1997","journal-title":"Appl. Opt."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2307\/3579621","article-title":"A Theoretical Study of Light Fractionation and Dose-Rate Effects in Photodynamic Therapy","volume":"147","author":"Pogue","year":"1997","journal-title":"Radiat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1364\/BOE.3.002142","article-title":"Interlesion differences in the local photodynamic therapy response of oral cavity lesions assessed by diffuse optical spectroscopies","volume":"3","author":"Rohrbach","year":"2012","journal-title":"Biomed. Opt. Express"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1097\/IGC.0000000000000497","article-title":"Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy","volume":"25","author":"Queniat","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1021\/acs.molpharmaceut.5b00260","article-title":"Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67","volume":"12","author":"Wang","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/j.1751-1097.2011.00943.x","article-title":"Aminolevulinic Acid-Photodynamic Therapy Combined with Topically Applied Vascular Disrupting Agent Vadimezan Leads to Enhanced Antitumor Responses","volume":"87","author":"Marrero","year":"2011","journal-title":"Photochem. Photobiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rohrbach, D.J., Rigual, N., Arshad, H., Tracy, E.C., Cooper, M.T., Shafirstein, G., Wilding, G., Merzianu, M., Baumann, H., and Henderson, B.W. (2016). Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma. J. Biomed. Opt., 21.","DOI":"10.1117\/1.JBO.21.1.018002"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"532368","DOI":"10.1155\/2008\/532368","article-title":"A Ratiometric Fluorescence Imaging System for Surgical Guidance","volume":"2008","author":"Moriyama","year":"2008","journal-title":"Adv. Opt. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1364\/OE.18.005580","article-title":"A fiberoptic reflectance probe with multiple source-collector separations to increase the dynamic range of derived tissue optical absorption and scattering coefficients","volume":"18","author":"Kim","year":"2010","journal-title":"Opt. Express"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1751-1097.1998.tb02521.x","article-title":"In vivo fluorescence spectroscopy and imaging for oncological applications","volume":"68","author":"Wagnieres","year":"1998","journal-title":"Photochem Photobiol"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wilson, N.A., Abu-Shumays, R., Lieberman, K., Akeson, M., and Dunbar, W.B. (2008, January 20\u201325). Feedback control of a DNA molecule tethered in a nanopore to repeatedly probe DNA-binding enzymes. Proceedings of the 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vancouver, BC, Canada.","DOI":"10.1109\/IEMBS.2008.4650519"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, A., Khurana, M., Moriyama, Y., and Wilson, B.C. (2010). Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements. J. Biomed. Opt., 15.","DOI":"10.1117\/1.3523616"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1751-1097.1998.tb09682.x","article-title":"Light dosimetry for intraperitoneal photodynamic therapy in a murine xenograft model of human epithelial ovarian carcinoma","volume":"68","author":"Lilge","year":"1998","journal-title":"Photochem. Photobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/lsm.10131","article-title":"A multispectral fluorescence imaging system: Design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors","volume":"32","author":"Yang","year":"2003","journal-title":"Lasers Surg. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"R61","DOI":"10.1088\/0031-9155\/53\/9\/R01","article-title":"The physics, biophysics and technology of photodynamic therapy","volume":"53","author":"Wilson","year":"2008","journal-title":"Phys. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1006\/gyno.2002.6793","article-title":"Laparoscopic Photodynamic Diagnosis of Ovarian Cancer Using 5-Aminolevulinic Acid in a Rat Model","volume":"87","author":"Chan","year":"2002","journal-title":"Gynecol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/lsm.20525","article-title":"In vivo quantification of fluorescent molecular markers in real-time by ratio imaging for diagnostic screening and image-guided surgery","volume":"39","author":"Bogaards","year":"2007","journal-title":"Lasers Surg. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1364\/BOE.6.003546","article-title":"Quantitative imaging of light-triggered doxorubicin release","volume":"6","author":"Kress","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sunar, U., Kress, J., Rohrbach, D.J., Carter, K.A., Luo, D., Shao, S., Lele, S., and Lovell, J.F. (2016, January 25\u201328). Light-triggered doxorubicin release quantified by spatial frequency domain imaging and diffuse optical spectroscopy. Proceedings of the Cancer Imaging and Therapy, Fort Lauderdale, FL, USA.","DOI":"10.1364\/CANCER.2016.JW4A.3"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1021\/acsnano.0c07680","article-title":"A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8+ T Cell Epitopes","volume":"15","author":"He","year":"2021","journal-title":"ACS Nano"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.21037\/jtd.2017.03.113","article-title":"Optical imaging of tissue obtained by transbronchial biopsies of peripheral lung lesions","volume":"9","author":"Harris","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.1158\/1078-0432.CCR-13-1735","article-title":"Photodynamic Therapy with 3-(1\u2032-Hexyloxyethyl) Pyropheophorbide a for Cancer of the Oral Cavity","volume":"19","author":"Rigual","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14969","DOI":"10.1364\/OE.18.014969","article-title":"Monitoring photobleaching and hemodynamic responses to HPPH-mediated photodynamic therapy of head and neck cancer: A case report","volume":"18","author":"Sunar","year":"2010","journal-title":"Opt. Express"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:38:55Z","timestamp":1759919935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031212"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031212","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.29.630668","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]}}}