Abstract

Photodynamic diagnosis (PDD) can improve diagnostic accuracy by using PDD agents such as 5-aminolevulinic acid (ALA). However, the weakness and photobleaching of fluorescence of PDD agents may lead to insufficient fluorescence visibility for the detection of cancer during resection operations. We focused on the “fluorescence enhancement effect” resulting from the addition of polyethylene glycol-modified titanium dioxide nanoparticles (TiO2-PEG NPs) to address these problems. The results showed that the combined administration of TiO2-PEG NPs and ALA could enhance and prolong fluorescence in bladder cancer cells, similar to in the mixture alone. It was suggested that the fluorescence enhancement was related to the accumulation of TiO2-PEG NPs in cells via endocytosis, causing the light scattering and enhancement of fluorescence. This fluorescence enhancement effect could be applicable for PDD.

Highlights

  • Photodynamic diagnosis (PDD), a fluorescence imaging method, is widely used for the intraoperative identification of cancer tissues [1,2,3]

  • PDD used for non-muscle-invasive bladder cancer detection can improve diagnostic accuracy using agents such as 5-aminolevulinic acid (ALA) or hexaminolevulinate hydrochloride [4,5]

  • In order to overcome these issues, it is possible to use combined administration with an antioxidant to reduce the photobleaching of protoporphyrin IX (PpIX) generated from ALA [8], prevent PpIX efflux by regulation of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter [9], and inhibit the reduction of the PpIX to heme by iron chelation [10]

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Summary

Introduction

Photodynamic diagnosis (PDD), a fluorescence imaging method, is widely used for the intraoperative identification of cancer tissues [1,2,3]. In order to overcome these issues, it is possible to use combined administration with an antioxidant to reduce the photobleaching of protoporphyrin IX (PpIX) generated from ALA [8], prevent PpIX efflux by regulation of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter [9], and inhibit the reduction of the PpIX to heme by iron chelation [10]. These previous studies were limited in terms of the chemical and biological properties of PpIX. We believe that a physical approach for enhancing and prolonging the fluorescence from PDD agents can be widely used across many types of PDD agent and together with other approaches

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