Abstract

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles’ photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.

Highlights

  • Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; combining effects in one agent normally requires a trade-off as the mechanisms interfere

  • Jablonski diagram helps clarify the basic principles of molecular photophysics, which is closely correlated with the functionality and efficacy of molecular optical agents for cancer diagnosis (e.g. fluorescence and photoacoustic (PA) imaging) and treatment (e.g. photodynamic therapy (PDT))[1,2,3]

  • On the basis of Jablonski diagram, there are generally three energy dissipation pathways that probably occur after a chromophore absorbs light[4,5,6]: (1) fluorescence emission; (2) intersystem crossing to a triplet excited state, followed by generation of phosphorescence and/or reactive oxygen species (ROS) and (3) thermal deactivation via non-radiation pathways

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Summary

Introduction

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; combining effects in one agent normally requires a trade-off as the mechanisms interfere. The integration of fluorescence and PA imaging modes decidedly enables precise diagnostic outcome by virtue of high sensitivity and imaging depth beyond the optical diffusion limit[18,19,20,21] For this purpose, there have been a number of investigations to date reported that one material with NIR absorption could be simultaneously used for dual-modality fluorescence and PA imaging[20, 21]. No such smart materials have been reported up to present In this contribution, we report a smart function-transformable nanoparticle (NP) based on a photo-controllable molecule dithienylethene (DTE)-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) for considerable improvement of cancer surgery outcomes. In vivo studies demonstrate that such intelligent NPs with controlled photophysical processes significantly boost the cancer surgery outcomes by harnessing the respective advantages of PA imaging, fluorescence imaging and PDT. This study provides a concept of function-transformable optical agent with maximized effectiveness of each function, and verifies its great clinical potential in cancer diagnosis and treatment during surgery

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