Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We...

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Bibliographic Details
Main Authors: Sandhya Clement, Ayad G. Anwer, Layla Pires, Jared Campbell, Brian C. Wilson, Ewa M. Goldys
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:International Journal of Molecular Sciences
Subjects:
reactive oxygen species
ROS
singlet oxygen
nanoparticles
radiation
RDT
Online Access:https://www.mdpi.com/1422-0067/22/12/6425
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spelling doaj-b4ac48b2f5884b798606a0f1754566802021-07-01T00:16:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226425642510.3390/ijms22126425Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA NanoparticlesSandhya Clement0Ayad G. Anwer1Layla Pires2Jared Campbell3Brian C. Wilson4Ewa M. Goldys5ARC Centre of Excellence in Nanoscale Biophotonics, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaARC Centre of Excellence in Nanoscale Biophotonics, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaPrincess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, CanadaARC Centre of Excellence in Nanoscale Biophotonics, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaPrincess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, CanadaARC Centre of Excellence in Nanoscale Biophotonics, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaRadiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.https://www.mdpi.com/1422-0067/22/12/6425reactive oxygen speciesROSsinglet oxygennanoparticlesradiationRDT
collection DOAJ
language English
format Article
sources DOAJ
author Sandhya Clement
Ayad G. Anwer
Layla Pires
Jared Campbell
Brian C. Wilson
Ewa M. Goldys
spellingShingle Sandhya Clement
Ayad G. Anwer
Layla Pires
Jared Campbell
Brian C. Wilson
Ewa M. Goldys
Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
International Journal of Molecular Sciences
reactive oxygen species
ROS
singlet oxygen
nanoparticles
radiation
RDT
author_facet Sandhya Clement
Ayad G. Anwer
Layla Pires
Jared Campbell
Brian C. Wilson
Ewa M. Goldys
author_sort Sandhya Clement
title Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
title_short Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
title_full Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
title_fullStr Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
title_full_unstemmed Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
title_sort radiodynamic therapy using tat peptide-targeted verteporfin-encapsulated plga nanoparticles
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-06-01
description Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.
topic reactive oxygen species
ROS
singlet oxygen
nanoparticles
radiation
RDT
url https://www.mdpi.com/1422-0067/22/12/6425
work_keys_str_mv AT sandhyaclement radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
AT ayadganwer radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
AT laylapires radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
AT jaredcampbell radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
AT briancwilson radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
AT ewamgoldys radiodynamictherapyusingtatpeptidetargetedverteporfinencapsulatedplgananoparticles
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