Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo

BMC Cancer

Mark C. Pierce¹  Michael Donzanti¹  Vidya Ganapathy¹  Shravani Barkund¹  Daniel Martin¹  Harini Kantamneni²  Charles M. Roth³  Prabhas V. Moghe³  Richard E. Riman⁴  Mei Chee Tan⁵  Xinyu Zhao⁵  Shuqing He⁵ 

[1] Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 08854, Piscataway, NJ, USA;Department of Chemical & Biochemical Engineering, Rutgers University, 98 Brett Road, 08854, Piscataway, NJ, USA;Department of Chemical & Biochemical Engineering, Rutgers University, 98 Brett Road, 08854, Piscataway, NJ, USA;Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 08854, Piscataway, NJ, USA;Department of Materials Science and Engineering, Rutgers University, 607 Taylor Road, 08854, Piscataway, NJ, USA;Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Rd, 487372, Singapore, Singapore;

关键词: Cancer metastasis;    Nanotechnology;    Short-wave infrared imaging;    Multiplexing;    Rare earths;   

DOI  :  10.1186/s12885-020-07604-8

来源: Springer

【 摘 要 】

BackgroundThe ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900–1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers.MethodsSWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes.ResultsEach of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging.ConclusionsThe results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

【 授权许可】

CC BY