Abstract
A novel, highly biocompatible, well soluble melanin-based probe obtained from the conjugation of melanin macromolecule to bovine serum albumin (BSA) was tested as a contrast agent for photoacoustic tumor imaging. Five soluble conjugates (PheoBSA A-E) were synthesized by oxidation of dopamine (DA) in the presence of variable amounts of BSA. All systems showed the similar size and absorbance spectra, being PheoBSA D (DA:BSA ratio 1:2) the one showing the highest photoacoustic efficiency. This system was then selected for the investigations as it showed a marked enhancement of the photoacoustic (PA) contrast in the tumor region upon iv injection. Biodistribution studies confirmed the accumulation of PheoBSA D within the tumor region and showed fast renal elimination, lack of cell toxicity, and good hemocompatibility. A higher PA contrast enhancement was observed in the case of PC3 prostate tumor xenograft when compared to the TS/A breast one, likely reflecting different vascularization/extravasation properties between the two tumor murine models. The improved PA properties shown by PheoBSA D allowed to set up a 3D dynamic contrast-enhanced (DCE) approach that demonstrated a persistent increase of the PA signal in the tumor region for a long period. Overall, the herein reported results demonstrate that PheoBSA D is a promising blood pool contrast agent for in vivo PA imaging, particularly useful for the set-up of 3D DCE-PA approaches to monitor tumor vascular properties.
Highlights
PhotoAcoustic Imaging (PAI) contrast is based on laser-generated ultrasounds [1], featuring concurrently the contrast ability of optical imaging and the high spatial resolution and penetration depth of ultrasounds [2]
The quinone compounds formed by the oxidation of DA react with the nucleophilic groups present in the protein and the growing melanic oligomers remain covalently linked to the protein, generating eumelanin-type conjugates (EuBSA)
The reported results show that PheoBSA D is a promising melanin‐based contrast agent for photoacoustic imaging
Summary
PhotoAcoustic Imaging (PAI) contrast is based on laser-generated ultrasounds [1], featuring concurrently the contrast ability of optical imaging and the high spatial resolution and penetration depth of ultrasounds [2]. Exogenous PAI contrast agents are based on several platforms, including small-molecule dyes like indocyanine green [14,15,16], eventually confined in silica nanoparticles [17,18], carbon nanoparticles [19,20,21], gold nanostructures [22,23,24,25,26], iron-based nanosystems [27], pyrroles [28,29] and biodegradable particles [30] All these newly developed CAs have been exploited for assessing several properties of the cancer microenvironment [31,32,33,34,35]. The design of less toxic nanoparticles based on endogenous molecules or optically active biodegradable materials attracted much attention in the last few years [10,30]
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