Abstract
Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (dDLS = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.
Highlights
Photoacoustic (PA) imaging is a growing bioimaging modality in which light-to-heat conversion mediated by light absorbers results in thermoelastic expansion of the surrounding tissues to lead to the emission of ultrasonic waves[1,2]
PMPC, poly(2-methacryloyloxyethylphosphorylcholine)[15,16,17], is highly biocompatible and selectively accumulated in tumor due to the EPR (Enhanced Permeability and Retention) effect[18], and 800RS is a hydrophilic near-infrared (NIR) cyanine dye. 800RS was used here after we surveyed the performance of various NIR cyanine dye conjugates including its indocyanine green (ICG) counterpart
ICG-conjugated polymer probes including ICG-PMPC, prepared by our group, bound nonspecifically to bovine serum albumin (BSA), which resulted in unavoidable accumulation of ICG-conjugated polymer probes in the liver[13]
Summary
Photoacoustic (PA) imaging is a growing bioimaging modality in which light-to-heat conversion mediated by light absorbers results in thermoelastic expansion of the surrounding tissues to lead to the emission of ultrasonic waves[1,2]. Since hemoglobin is an ideally PA-relevant endogenous chromophore, PA imaging is suited for high-resolution 3D (threedimensional) imaging of the vasculature of body tissues such as skin and implanted tumors[7,8,9] Another approach is to use genetic reporters such as fluorescent proteins and pigments as "semi-endogenous" contrast a gents. Recent attention has been paid to contrast agents in the so-called second NIR (1000–1700 nm) window (NIR-II) r egion[19,20] and their formulation[21] to allow higher spatial resolution, deeper penetration, and lower interference by tissue substrates with minimal autofluorescence Under these circumstances, PA imaging of tumors in animals has been intensely studied in recent years using various types of NIR and NIR-II21 contrast agents ( dyes[22,23,24], quantum d ots25, nanoparticles[26,27,28], semi-conducting p olymers[29], and so on30,31) in a variety of formulations and with diverse targeting s trategies[32]. The present technique represents a powerful new approach to both basic research and (pre)clinical studies of tumors
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