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Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy

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 ar...

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Autores principales: Stolarz, Amanda J., Chhetri, Bijay P., Borrelli, Michael J., Jenkins, Samir V., Jamshidi-Parsian, Azemat, Phillips, Joshua H., Fologea, Daniel, Gandy, Jay, Griffin, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569741/
https://www.ncbi.nlm.nih.gov/pubmed/36232973
http://dx.doi.org/10.3390/ijms231911662
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author Stolarz, Amanda J.
Chhetri, Bijay P.
Borrelli, Michael J.
Jenkins, Samir V.
Jamshidi-Parsian, Azemat
Phillips, Joshua H.
Fologea, Daniel
Gandy, Jay
Griffin, Robert J.
author_facet Stolarz, Amanda J.
Chhetri, Bijay P.
Borrelli, Michael J.
Jenkins, Samir V.
Jamshidi-Parsian, Azemat
Phillips, Joshua H.
Fologea, Daniel
Gandy, Jay
Griffin, Robert J.
author_sort Stolarz, Amanda J.
collection PubMed
description 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.
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spelling pubmed-95697412022-10-17 Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy Stolarz, Amanda J. Chhetri, Bijay P. Borrelli, Michael J. Jenkins, Samir V. Jamshidi-Parsian, Azemat Phillips, Joshua H. Fologea, Daniel Gandy, Jay Griffin, Robert J. Int J Mol Sci Article 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. MDPI 2022-10-02 /pmc/articles/PMC9569741/ /pubmed/36232973 http://dx.doi.org/10.3390/ijms231911662 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stolarz, Amanda J.
Chhetri, Bijay P.
Borrelli, Michael J.
Jenkins, Samir V.
Jamshidi-Parsian, Azemat
Phillips, Joshua H.
Fologea, Daniel
Gandy, Jay
Griffin, Robert J.
Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title_full Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title_fullStr Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title_full_unstemmed Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title_short Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy
title_sort liposome formulation for tumor-targeted drug delivery using radiation therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569741/
https://www.ncbi.nlm.nih.gov/pubmed/36232973
http://dx.doi.org/10.3390/ijms231911662
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