Abstract

.Photodynamic therapy (PDT), a spatially localized phototoxic therapy that involves irradiation of a photosensitizer (PS) with specific wavelengths of light, has shown exceptional promise in impacting cancer treatment outcomes, particularly oral cancer. To reduce PDT outcome variability, attempts toward image-guided personalized PDT are being pursued by monitoring PS uptake either via fluorescence or photoacoustic imaging (PAI), a nonionizing modality dependent on optical absorption properties of the tissue. PAI-guided PDT requires a near-infrared contrast agent for deep tissue imaging with minimal photobleaching effect. We evaluate the impact of PDT agent, benzoporphyrin derivative (BPD), on PAI agent indocyanine green (ICG) and vice versa, given that they have different optical absorption properties and singlet oxygen quantum yields for PDT. Specifically, we demonstrate in two oral squamous cell carcinoma lines (FaDu and SCC4) that ICG has minimal effect on BPD PDT efficacy when irradiated with either a continuous or pulsed laser. Furthermore, the impact of BPD on ICG photodegradation was monitored with PAI in tissue-mimicking phantoms. These studies inform us that the combination of BPD and ICG can be utilized for PAI-guided PDT. However, researchers need to consider the photodegradation effects of ICG in the presence of BPD when designing their drug delivery strategies for PAI-guided PDT.

Highlights

  • The past few decades have seen exponential growth in the utility of light for diagnosis and therapy of cancer

  • While the combination of indocyanine green (ICG) and benzoporphyrin derivative (BPD) is untried in a nanoformulation, in this study, we explore for the first time the mutual effects of ICG on BPD’s phototoxicity and BPD’s oxidation effect on ICG’s PA signal-generation capabilities

  • We evaluated the mutual impact of BPD and ICG on their photodynamic therapy (PDT) efficacy and PA signal stability

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Summary

Introduction

The past few decades have seen exponential growth in the utility of light for diagnosis and therapy of cancer. PDT’s worth as a mainstream therapy is currently being explored for various skin cancers, head and neck cancer, brain tumors, pulmonary and pleural mesothelial cancer, gastroenterological cancer, and urological disease, as well as for oral cancer.[6,7] Recently, the efficacy of PDT was demonstrated in oral cancer patients with early stage lesions. A single session of PDT treatment resulted in negative biopsies and excellent healing of the mucosa.[8] Despite promising results, one of the main hurdles for PDT in cancer has been variations in treatment outcome due to intertumor and intratumor heterogeneity in PS uptake due to irregular tumor vascular structure.[5,9,10] As the PS molecule is inherently a theranostic agent, Journal of Biomedical Optics

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