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Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma

BACKGROUND: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid...

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Autores principales: Zhou, Chong, Liu, Qin, Meng, Fanyan, Ding, Naiqing, Yan, Jing, Liu, Baorui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660045/
https://www.ncbi.nlm.nih.gov/pubmed/36388665
http://dx.doi.org/10.21037/jgo-22-951
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author Zhou, Chong
Liu, Qin
Meng, Fanyan
Ding, Naiqing
Yan, Jing
Liu, Baorui
author_facet Zhou, Chong
Liu, Qin
Meng, Fanyan
Ding, Naiqing
Yan, Jing
Liu, Baorui
author_sort Zhou, Chong
collection PubMed
description BACKGROUND: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo. METHODS: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation. Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD). RESULTS: Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 10(8) iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice. CONCLUSIONS: The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo.
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spelling pubmed-96600452022-11-15 Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma Zhou, Chong Liu, Qin Meng, Fanyan Ding, Naiqing Yan, Jing Liu, Baorui J Gastrointest Oncol Original Article BACKGROUND: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo. METHODS: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation. Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD). RESULTS: Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 10(8) iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice. CONCLUSIONS: The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo. AME Publishing Company 2022-10 /pmc/articles/PMC9660045/ /pubmed/36388665 http://dx.doi.org/10.21037/jgo-22-951 Text en 2022 Journal of Gastrointestinal Oncology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhou, Chong
Liu, Qin
Meng, Fanyan
Ding, Naiqing
Yan, Jing
Liu, Baorui
Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title_full Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title_fullStr Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title_full_unstemmed Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title_short Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma
title_sort modification of erythrocytes by internalizing arg-gly-asp (irgd) in boosting the curative effect of radiotherapy for gastric carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660045/
https://www.ncbi.nlm.nih.gov/pubmed/36388665
http://dx.doi.org/10.21037/jgo-22-951
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