Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/131359
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Type: Journal article
Title: Radiodynamic therapy using TAT peptide‐targeted Verteporfin‐encapsulated PLGA nanoparticles
Author: Clement, S.
Anwer, A.G.
Pires, L.
Campbell, J.
Wilson, B.C.
Goldys, E.M.
Citation: International Journal of Molecular Sciences, 2021; 22(12):6425-1-6425-15
Publisher: MDPI AG
Issue Date: 2021
ISSN: 1661-6596
1422-0067
Statement of
Responsibility: 
Sandhya Clement, Ayad G. Anwer, Layla Pires, Jared Campbell, Brian C. Wilson and Ewa M. Goldys
Abstract: 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.
Keywords: Reactive oxygen species; ROS; singlet oxygen; nanoparticles; radiation; RDT; radiosensitization; photosensitizer; PLGA; X-PDT; nuclear targeting; TAT peptide; verteporfin; radiation therapy; radiodynamic therapy
Rights: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
DOI: 10.3390/ijms22126425
Grant ID: http://purl.org/au-research/grants/arc/CE140100003
Published version: http://dx.doi.org/10.3390/ijms22126425
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