Oxygen-carrying polymer nanoconstructs for radiodynamic therapy of deep hypoxic malignant tumors

Sandhya Clement*, Anna Guller, Saabah B. Mahbub, Ewa M. Goldys

*Corresponding author for this work

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Abstract

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated hypoxia that results in low availability of oxygen for the generation of sufficient amounts of ROS. Herein, a novel nanoparticle drug formulation for RDT, which addresses the problem of low oxygen availability, is reported. It consists of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with a PS drug verteporfin (VP), and the clinically approved oxygen-carrying molecule, perfluorooctylbromide (PFOB). When triggered by X-rays (4 Gy), under both normoxic and hypoxic conditions, PLGA–VP–PFOB nanoconstructs (NCs) induced a significant increase of the ROS production compared with matching PLGA–VP nanoparticles. The RDT with NCs effectively killed ~60% of human pancreatic cancer cells in monolayer cultures, and almost completely suppressed the outgrowth of tumor cells in 2-weeks clonogenic assay. In a 3D engineered model of pancreatic cancer metastasis to the liver, RDT with NCs destroyed ~35% of tumor cells, demonstrating an exceptional efficiency at a tissue level. These results show that PLGA–VP–PFOB is a promising agent for RDT of deep-seated hypoxic tumors.

Original languageEnglish
Article number322
Pages (from-to)1-24
Number of pages24
JournalBiomedicines
Volume9
Issue number3
DOIs
Publication statusPublished - 22 Mar 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) [include year if part of copyright statement]. 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

  • 3D tumor model in vitro
  • Hypoxia
  • Oxygen-carrying polymer nanoparticles
  • Pancreatic cancer
  • Radiodynamic therapy

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