Journal
ACS NANO
Volume 7, Issue 3, Pages 2541-2550Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn3058642
Keywords
tumor hypoxia; nanoparticle; photothermal therapy; photodynamic therapy; porphyrin; porphysome
Categories
Funding
- MaRS Innovation
- Canadian Institute of Health Research
- Canadian Space Agency
- Prostate Cancer foundation of Canada
- Natural Sciences and Engineering Research Council of Canada
- Canadian Foundation for Innovation
- Princess Margaret Cancer Center Foundation
- Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research
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Tumor hypoxia is increasingly being recognized as a characteristic feature of solid tumors and significantly complicates many treatments based on radio-, chemo-, and phototherapies. While photodynamic therapy (PDT) Is based on photosensitizer interactions with diffused oxygen, photothermal therapy (PTT) has emerged as a new phototherapy that is predicted to be independent of oxygen levels within tumors. It has been challenging to meaningfully compare these two modalities due to differences in contrast agents and irradiation parameters, and no comparative In vivo studies have been performed until now. Here, by making use of recently developed nanostructured self-quenched porphysome nanoparticles, we were able to directly compare PDT and PTT using matched light doses and matched porphyrin photosensitizer doses (with the photosensitizer being effective for either PTT or PDT based on the existence of nanostructure or not). Therefore, we demonstrated the nanostructure-driven conversion from the PDT singlet oxygen generating mechanism of porphyrin to a completely thermal mechanism, ideal for PTT enhancement. Using a novel hypoxia tumor model, we determined that nanostructured porphyrin PTT enhancers are advantageous to overcome hypoxic conditions to achieve effective ablation of solid tumors.
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