Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging

Jeanne E. Lemaster; Zhao Wang; Ali Hariri; Fang Chen; Ziying Hu; Yuran Huang; Christopher V. Barback; Richard Cochran; Nathan C. Gianneschi; Jesse V. Jokerst

doi:10.1021/acs.chemmater.8b04333

Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging

Jeanne E. Lemaster, Zhao Wang, Ali Hariri, Fang Chen, Ziying Hu, Yuran Huang, Christopher V. Barback, Richard Cochran, Nathan C. Gianneschi, Jesse V. Jokerst^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

Abstract

In this paper, we show 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 labeling 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. Cellular uptake was confirmed with bright-field optical and transmission electron microscopy. The Gd(III)-SMNP-labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found that the photoacoustic signal increased as the cell number increased (R² = 0.96), indicating that such an approach could be employed to discriminate between stem cell populations with a limit of detection of 2.3 × 10⁴ cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.

Original language	English (US)
Pages (from-to)	251-259
Number of pages	9
Journal	Chemistry of Materials
Volume	31
Issue number	1
DOIs	https://doi.org/10.1021/acs.chemmater.8b04333
State	Published - Jan 8 2019

Funding

*E-mail: [email protected]. ORCID Fang Chen: 0000-0002-6675-5508 Richard Cochran: 0000-0002-0736-6529 Nathan C. Gianneschi: 0000-0001-9945-5475 Jesse V. Jokerst: 0000-0003-2829-6408 Present Address ○Currently affiliated with Thermo Fisher Scientific, Analytical Instrumentation Group (R.C.). Author Contributions ◆J.E.L. and Z.W. contributed equally to this work. Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Funding J.E.L. acknowledges funding from the National Institutes of Health (NIH) Institutional National Research Service Award T32 CA153915, Cancer Researchers in Nanotechnology. J.V.J. acknowledges funding from the NIH (Grants R00 HL117048 and DP2 HL137187) and infrastructure from Grant S10 OD021821. This work was performed, in part, at the San Diego Nanotechnology Infrastructure of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS-1542148). This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IINNotes. Notes The authors declare no competing financial interest.

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering
Materials Chemistry

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title = "Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging",

abstract = "In this paper, we show 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 labeling 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. Cellular uptake was confirmed with bright-field optical and transmission electron microscopy. The Gd(III)-SMNP-labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found that the photoacoustic signal increased as the cell number increased (R2 = 0.96), indicating that such an approach could be employed to discriminate between stem cell populations with a limit of detection of 2.3 × 104 cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.",

author = "Lemaster, {Jeanne E.} and Zhao Wang and Ali Hariri and Fang Chen and Ziying Hu and Yuran Huang and Barback, {Christopher V.} and Richard Cochran and Gianneschi, {Nathan C.} and Jokerst, {Jesse V.}",

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Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging

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