Melanin is a natural pigment with myriad functions arising from its chemical structure including metal ion chelation, photo-protection, free radical quenching, and coloration. In humans, melanins can serve as a biomarker for melanoma and Parkinson’s disease. To exploit these properties, several groups have reported synthetic melanin nanoparticles (SMNPs) synthesized by the auto-oxidation of dopamine or L-3,4-dihydroxyphenylalanine to be used as contrast agents. We showed that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labelling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells (hMSCs). Cellular uptake was confirmed with bright field optical and transmission electron microscopy. The Gd(III)-SMNP labeled stem cells expressed the stem cell surface markers CD73, CD90, and CD105 and continued to proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found the photoacoustic signal increased as cell number increased (R2 = 0.96) indicating that such an approach could be employed to quantify stem cells with a limit of detection of 2.3 x 104 cells. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.

Gadolinium doping enhances the photoacoustic signal of synthetic melanin nanoparticles: Dual modality contrast agent for stem cell imaging

2019 Fall National Meeting

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