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 highenergy 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.
| Original language | English |
|---|---|
| Article number | 6425 |
| Pages (from-to) | 1-15 |
| Number of pages | 15 |
| Journal | International Journal of Molecular Sciences |
| Volume | 22 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 15 Jun 2021 |
Bibliographical note
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- Nanoparticles
- Nuclear targeting
- Photosensitizer
- PLGA
- Radiation
- Radiation therapy
- Radiodynamic therapy
- Radiosensitization
- RDT
- Reactive oxygen species
- ROS
- Singlet oxygen
- TAT peptide
- Verteporfin
- X‐PDT