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Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer

[Image: see text] In this work, we brought together two existing clinical techniques used in cancer treatment—X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially t...

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Autores principales: Deng, Wei, McKelvey, Kelly J., Guller, Anna, Fayzullin, Alexey, Campbell, Jared M., Clement, Sandhya, Habibalahi, Abbas, Wargocka, Zofia, Liang, Liuen, Shen, Chao, Howell, Viive Maarika, Engel, Alexander Frank, Goldys, Ewa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256935/
https://www.ncbi.nlm.nih.gov/pubmed/32490188
http://dx.doi.org/10.1021/acscentsci.9b01121
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author Deng, Wei
McKelvey, Kelly J.
Guller, Anna
Fayzullin, Alexey
Campbell, Jared M.
Clement, Sandhya
Habibalahi, Abbas
Wargocka, Zofia
Liang, Liuen
Shen, Chao
Howell, Viive Maarika
Engel, Alexander Frank
Goldys, Ewa M.
author_facet Deng, Wei
McKelvey, Kelly J.
Guller, Anna
Fayzullin, Alexey
Campbell, Jared M.
Clement, Sandhya
Habibalahi, Abbas
Wargocka, Zofia
Liang, Liuen
Shen, Chao
Howell, Viive Maarika
Engel, Alexander Frank
Goldys, Ewa M.
author_sort Deng, Wei
collection PubMed
description [Image: see text] In this work, we brought together two existing clinical techniques used in cancer treatment—X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2–5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).
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spelling pubmed-72569352020-06-01 Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer Deng, Wei McKelvey, Kelly J. Guller, Anna Fayzullin, Alexey Campbell, Jared M. Clement, Sandhya Habibalahi, Abbas Wargocka, Zofia Liang, Liuen Shen, Chao Howell, Viive Maarika Engel, Alexander Frank Goldys, Ewa M. ACS Cent Sci [Image: see text] In this work, we brought together two existing clinical techniques used in cancer treatment—X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2–5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death). American Chemical Society 2020-04-24 2020-05-27 /pmc/articles/PMC7256935/ /pubmed/32490188 http://dx.doi.org/10.1021/acscentsci.9b01121 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Deng, Wei
McKelvey, Kelly J.
Guller, Anna
Fayzullin, Alexey
Campbell, Jared M.
Clement, Sandhya
Habibalahi, Abbas
Wargocka, Zofia
Liang, Liuen
Shen, Chao
Howell, Viive Maarika
Engel, Alexander Frank
Goldys, Ewa M.
Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title_full Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title_fullStr Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title_full_unstemmed Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title_short Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer
title_sort application of mitochondrially targeted nanoconstructs to neoadjuvant x-ray-induced photodynamic therapy for rectal cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256935/
https://www.ncbi.nlm.nih.gov/pubmed/32490188
http://dx.doi.org/10.1021/acscentsci.9b01121
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