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

Deng, W; McKelvey, KJ; Guller, A; Fayzullin, A; Campbell, JM; Clement, S; Habibalahi, A; Wargocka, Z; Liang, L; Shen, C; Howell, VM; Engel, AF; Goldys, EM

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

McKelvey, KJ Guller, A Fayzullin, A Campbell, JM Clement, S Habibalahi, A Wargocka, Z Liang, L Shen, C Howell, VM Engel, AF Goldys, EM

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: ACS central science, 2020, 6, (5), pp. 715-726
Issue Date:: 2020-05

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Field	Value	Language
dc.contributor.author	Deng, W https://orcid.org/0000-0002-9413-0978
dc.contributor.author	McKelvey, KJ
dc.contributor.author	Guller, A
dc.contributor.author	Fayzullin, A
dc.contributor.author	Campbell, JM
dc.contributor.author	Clement, S
dc.contributor.author	Habibalahi, A
dc.contributor.author	Wargocka, Z
dc.contributor.author	Liang, L
dc.contributor.author	Shen, C
dc.contributor.author	Howell, VM
dc.contributor.author	Engel, AF
dc.contributor.author	Goldys, EM
dc.date.accessioned	2021-07-04T23:38:16Z
dc.date.available	2021-07-04T23:38:16Z
dc.date.issued	2020-05
dc.identifier.citation	ACS central science, 2020, 6, (5), pp. 715-726
dc.identifier.issn	2374-7943
dc.identifier.issn	2374-7951
dc.identifier.uri	http://hdl.handle.net/10453/149814
dc.description.abstract	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).
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation.ispartof	ACS central science
dc.relation.isbasedon	10.1021/acscentsci.9b01121
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	03 Chemical Sciences
dc.title	Application of Mitochondrially Targeted Nanoconstructs to Neoadjuvant X-ray-Induced Photodynamic Therapy for Rectal Cancer.
dc.type	Journal Article
utslib.citation.volume	6
utslib.location.activity	United States
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0903 Biomedical Engineering
utslib.for	03 Chemical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
dc.date.updated	2021-07-04T23:38:10Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	6
utslib.citation.issue	5

Abstract:

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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http://hdl.handle.net/10453/149814