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Biomaterials. 2018 Aug;175:30-43. doi: 10.1016/j.biomaterials.2018.05.021. Epub 2018 May 15.

Ultra-small nanocluster mediated synthesis of Nd3+-doped core-shell nanocrystals with emission in the second near-infrared window for multimodal imaging of tumor vasculature.

Author information

1
Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
2
Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Wollongong, NSW 2500, Australia.
3
Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China; Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Wollongong, NSW 2500, Australia. Electronic address: zhenli@suda.edu.cn.

Abstract

In-vivo intravital short wavelength infrared (SWIR, 1000-2300 nm) fluorescence imaging has attracted considerable attention in the imaging of tumor vasculature due to its low background, high sensitivity, and deep penetration. It can noninvasively provide dynamic feedback on the tumorigenesis, growth, necrosis and metastasis. Herein, monodisperse Nd3+-doped core-shell downconversion luminescent nanocrystals with strong emission in the second near-infrared (NIR II) window, strong temperature-dependent paramagnetism and fast attenuation to X-rays were prepared from ultra-small nanoclusters. The use of nanoclusters resulted in very uniform bright nanocrystals with a relative quantum yield comparable to the standard dye IR-26. These bright NIR nanocrystals were modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] to endow with excellent water-solubility, biocompatibility and a blood circulation half-life of 5.9 h. They were then successfully used to demonstrate the variation of tumor vasculature with tumor progression from tumorigenesis, growth, to necrosis in the subcutaneous breast tumor through the NIR II fluorescence imaging. They were also used as contrast agent of magnetic resonance imaging (MRI) and X-ray computed tomography (CT) imaging of tumor to provide complementary anatomic structure. Their great potential in NIR II imaging of tumor was further demonstrated with an orthotopic breast tumor. Their in-vivo biosafety was also investigated by hemanalysis and histological analyses.

KEYWORDS:

Computed tomography imaging; Magnetic resonance imaging; NIR II fluorescence imaging; Nd(3+)-doped core-shell nanocrystals; Tumor vasculature

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