Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Multicore Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo

临床前影像学 体内 多路复用 材料科学 分子成像 拉曼光谱 离体 拉曼散射 纳米技术 生物医学工程 光学 计算机科学 医学 生物 物理 电信 生物技术
作者
Jung Ho Yu,Idan Steinberg,Ryan M. Davis,Andrey V. Malkovskiy,Aimen Zlitni,Rochelle Karina Radzyminski,Kyung Oh Jung,Daniel Tan Chung,Luis Dan Curet,Aloma D’Souza,Edwin Chang,Jarrett Rosenberg,Jos L. Campbell,Hadas Frostig,Seung Min Park,Guillem Pratx,Craig S. Levin,Sanjiv S. Gambhir
出处
期刊:ACS Nano [American Chemical Society]
卷期号:15 (12): 19956-19969 被引量:18
标识
DOI:10.1021/acsnano.1c07470
摘要

In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.
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