Oxygen Generating Nanoparticles for Improved Photodynamic Therapy of Hypoxic Tumours.

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Abstract

Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitisier drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH 7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p
LanguageEnglish
Pages333-340
JournalJournal of Controlled Release
Volume264
Early online date8 Sep 2017
DOIs
Publication statusE-pub ahead of print - 8 Sep 2017

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Photochemotherapy
Nanoparticles
Oxygen
Polymers
Neoplasms
Reactive Oxygen Species
Light
Pharmaceutical Preparations

Keywords

  • Hypoxia
  • calcium peroxide
  • Photodynamic Therapy
  • pancreatic cancer.

Cite this

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title = "Oxygen Generating Nanoparticles for Improved Photodynamic Therapy of Hypoxic Tumours.",
abstract = "Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitisier drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH 7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p",
keywords = "Hypoxia, calcium peroxide, Photodynamic Therapy, pancreatic cancer.",
author = "J Callan and Y Sheng and Heather Nesbitt and Bridgeen Callan and AP McHale",
year = "2017",
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journal = "Journal of Controlled Release",
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T1 - Oxygen Generating Nanoparticles for Improved Photodynamic Therapy of Hypoxic Tumours.

AU - Callan, J

AU - Sheng, Y

AU - Nesbitt, Heather

AU - Callan, Bridgeen

AU - McHale, AP

PY - 2017/9/8

Y1 - 2017/9/8

N2 - Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitisier drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH 7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p

AB - Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitisier drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH 7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p

KW - Hypoxia

KW - calcium peroxide

KW - Photodynamic Therapy

KW - pancreatic cancer.

U2 - 10.1016/j.jconrel.2017.09.004

DO - 10.1016/j.jconrel.2017.09.004

M3 - Article

VL - 264

SP - 333

EP - 340

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -