Abstract

Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

Highlights

  • Photoacoustic (PA) imaging is an emerging technique based on the use of laser generated ultrasound, which holds great promise for visualizing anatomical structures and physiological changes in vivo

  • These are based on novel indigoid π-conjugated organic semiconductors with a high extinction coefficient, narrow band gap, and with absorption maxima located in the near-infrared in the “optical window” of low absorption of endogenous chromophores within human tissue

  • These polymers were coformulated with DPPC to give stable nanoparticles of consistent size and zeta potential, good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients up to three times higher than previously reported Semiconducting polymer nanoparticles (SPNs)

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Summary

Introduction

Photoacoustic (PA) imaging is an emerging technique based on the use of laser generated ultrasound, which holds great promise for visualizing anatomical structures and physiological changes in vivo It combines the advantages of ultrasound imaging (submillimeter spatial resolution with deep tissue imaging penetration) with the high contrast and specificity of optical imaging.[1] It is noninvasive and does not require the use of ionizing radiation, and has significant potential for the clinical and preclinical study of conditions such as breast, head and neck, melanoma, colorectal, prostate, and ovarian cancers, and cardiovascular disease.[2] Endogenous PA image contrast is based on optical absorption provided by naturally occurring chromophores, such as lipids or hemoglobin, the latter enabling exquisite images of the vasculature to be acquired.[3] many cells and tissues are weakly absorbing at visible and nearinfrared wavelengths and require labeling with exogenous contrast agents to provide PA image contrast. This range is known as the optical window of tissue, due to the low absorption of water and hemoglobin in this region

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