X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs.

Clement, S; Chen, W; Deng, W; Goldys, EM

X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs.

Clement, S Chen, W Deng, W

Goldys, EM

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Publisher:: DOVE MEDICAL PRESS LTD
Publication Type:: Journal Article
Citation:: Int J Nanomedicine, 2018, 13, pp. 3553-3570
Issue Date:: 2018

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Field	Value	Language
dc.contributor.author	Clement, S
dc.contributor.author	Chen, W
dc.contributor.author	Deng, W https://orcid.org/0000-0002-9413-0978
dc.contributor.author	Goldys, EM
dc.date.accessioned	2022-09-08T01:52:59Z
dc.date.available	2022-09-08T01:52:59Z
dc.date.issued	2018
dc.identifier.citation	Int J Nanomedicine, 2018, 13, pp. 3553-3570
dc.identifier.issn	1176-9114
dc.identifier.issn	1178-2013
dc.identifier.uri	http://hdl.handle.net/10453/161516
dc.description.abstract	INTRODUCTION: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. MATERIALS AND METHODS: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. RESULTS AND DISCUSSION: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. CONCLUSION: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	DOVE MEDICAL PRESS LTD
dc.relation	http://purl.org/au-research/grants/arc/CE140100003
dc.relation.ispartof	Int J Nanomedicine
dc.relation.isbasedon	10.2147/IJN.S164967
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1007 Nanotechnology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Nanoscience & Nanotechnology
dc.subject.mesh	Biocompatible Materials
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Survival
dc.subject.mesh	Folic Acid
dc.subject.mesh	Humans
dc.subject.mesh	Image Processing, Computer-Assisted
dc.subject.mesh	Lactic Acid
dc.subject.mesh	Nanoparticles
dc.subject.mesh	Particle Size
dc.subject.mesh	Photochemotherapy
dc.subject.mesh	Photosensitizing Agents
dc.subject.mesh	Polyglycolic Acid
dc.subject.mesh	Polylactic Acid-Polyglycolic Acid Copolymer
dc.subject.mesh	Porphyrins
dc.subject.mesh	Singlet Oxygen
dc.subject.mesh	Static Electricity
dc.subject.mesh	Verteporfin
dc.subject.mesh	X-Rays
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	Singlet Oxygen
dc.subject.mesh	Lactic Acid
dc.subject.mesh	Porphyrins
dc.subject.mesh	Folic Acid
dc.subject.mesh	Polyglycolic Acid
dc.subject.mesh	Photosensitizing Agents
dc.subject.mesh	Biocompatible Materials
dc.subject.mesh	Photochemotherapy
dc.subject.mesh	Cell Survival
dc.subject.mesh	Particle Size
dc.subject.mesh	X-Rays
dc.subject.mesh	Image Processing, Computer-Assisted
dc.subject.mesh	Nanoparticles
dc.subject.mesh	Static Electricity
dc.subject.mesh	Polylactic Acid-Polyglycolic Acid Copolymer
dc.subject.mesh	Verteporfin
dc.title	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	New Zealand
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1007 Nanotechnology
utslib.for	1115 Pharmacology and Pharmaceutical 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	open_access	*
dc.date.updated	2022-09-08T01:52:53Z
pubs.publication-status	Published online
pubs.volume	13

Abstract:

INTRODUCTION: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. MATERIALS AND METHODS: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. RESULTS AND DISCUSSION: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. CONCLUSION: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.

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http://hdl.handle.net/10453/161516