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NIRF Nanoprobes for Cancer Molecular Imaging: Approaching Clinic

https://doi.org/10.1016/j.molmed.2020.02.003Get rights and content

Highlights

  • NIRF imaging is a highly versatile molecular imaging modality with high detection sensitivity, resolution, and convenience for in vivo applications. Recent rapid advances in research in this field provide powerful techniques for cancer imaging and management.

  • The emission wavelength at the second NIR window has been used for in vivo imaging and led to a plethora of NIR-II nanoprobes with high imaging performance. New illumination strategies without the use of lasers have been actively pursued, resulting in the discovery of numerous self-illuminating nanoprobes, chemiluminescent nanoprobes, and radioluminescent nanoprobes.

  • A broad range of NIRF nanoprobes have been engineered and developed based on novel nanomaterials and design concepts and the multifunctional nature of nanoplatforms has been applied to construct new multimodality imaging and theranostic nanoprobes.

Near-IR fluorescence imaging (NIRFI) is a highly promising technique for improving cancer theranostics in the era of precision medicine. Through the combination with cutting-edge bionanotechnologies, the potential of NIRFI can be greatly broadened. A variety of novel NIRF nanoprobes has been developed with ultimate goals of addressing unmet medical needs. Here, we present recent breakthroughs on the fundamental aspects of NIRFI, such as imaging at long wavelengths (1000–1700 nm), and the use of new approaches (X-rays, chemiluminescence, radioluminescence, etc.) for the excitation of novel nanoprobes. Within two decades, research on NIRF nanoprobes has translated to clinical trials and it will further translate to cancer management.

Section snippets

Molecular Imaging and Nanotechnology

Molecular imaging (MI, see Glossary) represents one of the highly dynamic research areas in biomedicine and is an essential component, along with various omics such as genomics, proteomics, and metabolomics and big-data techniques, of the realization of precision medicine. With the goal of curing cancer or taming cancer into a chronic, manageable disease, MI has been extensively studied by scientists and heavily invested in by governments and funding agencies during the past two decades,

Breakthrough on NIRFI Windows and Illumination Strategies

OI can be performed using excitation and emission light in the ranges of the visible window (390–700 nm), the first NIR window (NIR-I) (700–900 nm), and the second NIR window (NIR-II) (1000-1700 nm). NIRFI refers to the use of a light-detecting device to capture the emission fluorescence (700–1700 nm) generated from laser illumination of contrast agents in a living subject (either an endogenous molecule or an exogenous molecular probe administered into the body). For imaging of diseases,

NIRF Nanoprobes for Cancer Imaging

Although either endogenous fluorescent molecules such as reduced NADH and porphyrins (heme pathway derivatives; e.g., hemoglobin) or exogenous molecular probes can be used for OI, the latter are much more important and play prominent roles because of their high potential to fulfill a diverse range of medical needs [8,63., 64., 65.]. The development of molecular probes, including nanoprobes, for in vivo NIRFI is a highly active and diverse research area and novel chemistry, materials, and

NIRF-Based Multimodality Imaging

NIRFI has advantages and limitations and needs to be integrated with other modalities to broaden its applications (Box 1). For instance, NIRFI has limited tissue penetration depth and is more suitable for imaging of superficial or local tissues, while PET has deep-tissue imaging capability. Dual-modality NIRFI/PET can realize preoperative whole-body imaging using PET and intraoperative local disease imaging using NIRFI at high sensitivity and in real time. Modalities such as PET, SPECT, NIRFI,

Clinical Translation of NIRF Nanoprobes

Currently, around 50 nanopharmaceuticals including liposomes, polymers, nanocrystals, inorganic compounds, micelles, and protein NPs are available as approved drugs for various indications, and even more (>60) are in clinical trials as investigational drugs, demonstrating the high promise of using nanoplatforms for the development of novel treatment regimens and NIRFI [93]. Although there is no NIRFI nanoprobe approved by the FDA, several are under clinical evaluation. Among them, indocyanine

Concluding Remarks

Tremendous progress has been made in the development of NIRF nanoprobes for clinical translation. Although a bright future is expected, several challenges remain in order to pave the road in a field without much exploration. Many questions remain to be addressed in NIRF nanoprobe development (see Outstanding Questions). One of the most urgent needs is to prove the medical value of NIRF nanoprobes using concrete clinical data. The NIRF nanoprobes cRGDY-PEG-Cy5.5-C dots and ONM-100 are in

Acknowledgments

This study was partially supported by the National Key Research and Development Program of China (2017YFA0205200, 2016YFC0102600), the National Natural Science Foundation of China (NSFC) (21877057, 81930053, 61622117), the Beijing Nova Program (Z181100006218046), the Jiangmen Program for Innovative Research Team (2018630100180019806), and the Department of Radiology, Stanford University.

Glossary

Bioluminescence resonance energy transfer (BRET)
uses Förster resonance energy transfer from a bioluminescent donor to an acceptor with the aid of a substrate. The donor enzyme can be luciferase or its mutants, such as Renilla luciferase (Luc8), and the substrate can be luciferin, coelenterazine, etc. It converts chemical energy from a reaction catalyzed by the enzyme into light rather than the absorption of excitation photons.
Cerenkov excited luminescence imaging (CELI) or CR energy transfer

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