{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:12:51Z","timestamp":1774069971295,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,2]],"date-time":"2022-10-02T00:00:00Z","timestamp":1664668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health, including the National Cancer Institute","award":["75N91020C00054"],"award-info":[{"award-number":["75N91020C00054"]}]},{"name":"National Institutes of Health, including the National Cancer Institute","award":["P20-GM109005"],"award-info":[{"award-number":["P20-GM109005"]}]},{"name":"National Institutes of Health, including the National Cancer Institute","award":["1554166"],"award-info":[{"award-number":["1554166"]}]},{"name":"National Institute of General Medical Sciences Centers of Biomedical Research Excellence the Center","award":["75N91020C00054"],"award-info":[{"award-number":["75N91020C00054"]}]},{"name":"National Institute of General Medical Sciences Centers of Biomedical Research Excellence the Center","award":["P20-GM109005"],"award-info":[{"award-number":["P20-GM109005"]}]},{"name":"National Institute of General Medical Sciences Centers of Biomedical Research Excellence the Center","award":["1554166"],"award-info":[{"award-number":["1554166"]}]},{"name":"National Science Foundation","award":["75N91020C00054"],"award-info":[{"award-number":["75N91020C00054"]}]},{"name":"National Science Foundation","award":["P20-GM109005"],"award-info":[{"award-number":["P20-GM109005"]}]},{"name":"National Science Foundation","award":["1554166"],"award-info":[{"award-number":["1554166"]}]},{"name":"Osher Lifelong Learning Institute at Boise State University","award":["75N91020C00054"],"award-info":[{"award-number":["75N91020C00054"]}]},{"name":"Osher Lifelong Learning Institute at Boise State University","award":["P20-GM109005"],"award-info":[{"award-number":["P20-GM109005"]}]},{"name":"Osher Lifelong Learning Institute at Boise State University","award":["1554166"],"award-info":[{"award-number":["1554166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.<\/jats:p>","DOI":"10.3390\/ijms231911662","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy"],"prefix":"10.3390","volume":"23","author":[{"given":"Amanda J.","family":"Stolarz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Rejuvenics Technologies, LLC, Perryville, AR 72126, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijay P.","family":"Chhetri","sequence":"additional","affiliation":[{"name":"Rejuvenics Technologies, LLC, Perryville, AR 72126, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1496-2035","authenticated-orcid":false,"given":"Samir V.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azemat","family":"Jamshidi-Parsian","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua H.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Rejuvenics Technologies, LLC, Perryville, AR 72126, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Fologea","sequence":"additional","affiliation":[{"name":"Department of Physics and Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Gandy","sequence":"additional","affiliation":[{"name":"Rejuvenics Technologies, LLC, Perryville, AR 72126, USA"},{"name":"Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-2958","authenticated-orcid":false,"given":"Robert J.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Rejuvenics Technologies, LLC, Perryville, AR 72126, USA"},{"name":"Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.7150\/thno.55163","article-title":"Externally Triggered Smart Drug Delivery System Encapsulating Idarubicin Shows Superior Kinetics and Enhances Tumoral Drug Uptake and Response","volume":"11","author":"Lu","year":"2021","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1158\/1535-7163.MCT-09-0856","article-title":"Effect of Pazopanib on Tumor Microenvironment and Liposome Delivery","volume":"9","author":"Tailor","year":"2010","journal-title":"Mol. 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