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      Near‐Infrared‐II Molecular Dyes for Cancer Imaging and Surgery

      1 , 1 , 2 , 1 , 2
      Advanced Materials
      Wiley

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          Abstract

          Fluorescence bioimaging affords a vital tool for both researchers and surgeons to molecularly target a variety of biological tissues and processes. This review focuses on summarizing organic dyes emitting at a biological transparency window termed the near-infrared-II (NIR-II) window, where minimal light interaction with the surrounding tissues allows photons to travel nearly unperturbed throughout the body. NIR-II fluorescence imaging overcomes the penetration/contrast bottleneck of imaging in the visible region, making it a remarkable modality for early diagnosis of cancer and highly sensitive tumor surgery. Due to their convenient bioconjugation with peptides/antibodies, NIR-II molecular dyes are desirable candidates for targeted cancer imaging, significantly overcoming the autofluorescence/scattering issues for deep tissue molecular imaging. To promote the clinical translation of NIR-II bioimaging, advancements in the high-performance small-molecule derived probes are critically important. We discuss here molecules with clinical potential for NIR-II imaging, summarizing the synthesis and chemical structures of NIR-II dyes, chemical and optical properties of NIR-II dyes, bioconjugation and biological behavior of NIR-II dyes, whole body imaging with NIR-II dyes for cancer detection and surgery, as well as NIR-II fluorescence microscopy imaging. We will also propose a key perspective on the direction of near-infrared-II molecular dyes for cancer imaging and surgery.

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          Most cited references94

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          On the mechanisms of biocompatibility.

          The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.
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            In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy

            Monoclonal antibodies (mAbs) targeting the immune checkpoint anti–programmed cell death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment of some cancers; however, these drugs are not always effective, and we still have a limited understanding of the mechanisms that contribute to their efficacy or lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1 mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs effectively bind PD-1+ tumor-infiltrating CD8+ T cells at early time points after administration. However, this engagement is transient, and aPD-1 mAbs are captured within minutes from the T cell surface by PD-1– tumor-associated macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both on the drug’s Fc domain glycan and on Fc receptors (FcRs) expressed by host myeloid cells and extend these findings to the human setting. Finally, we demonstrate that in vivo blockade of FcRs before aPD-1 mAb administration substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8+ T cells and enhances immunotherapy-induced tumor regression in mice. These investigations yield insight into aPD-1 target engagement in vivo and identify specific Fc/FcR interactions that can be modulated to improve checkpoint blockade therapy.
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              Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics.

              The development of fluorophores and molecular probes for the second near-infrared biological window (NIR-II, 1000-1700 nm) represents an important, newly emerging and dynamic field in molecular imaging, chemical biology and materials chemistry. Because of reduced scattering, minimal absorption and negligible autofluorescence, NIR-II imaging provides high resolution, a high signal-to-noise ratio, and deep tissue penetration capability. Among various state-of-the-art bioimaging modalities, one of the greatest challenges in developing novel probes is to achieve both high resolution and sensitivity. The chemical design and synthesis of NIR-II fluorophores suitable for multimodal imaging is thus emerging as a new and powerful strategy for obtaining high-definition images. NIR-II fluorophores may convert NIR-II photons into heat for photothermal therapy and be excited by NIR-II light to produce singlet oxygen for photodynamic therapy. The presence of simultaneous diagnostic and therapeutic capabilities in a single probe can be used for precise treatment. In this review, we have focused on recent advances in the chemical design and synthesis of NIR-II fluorophores from small organic molecules to organic and inorganic nanoparticles, and we have further discussed recent advances and key operational differences in reported NIR-II imaging systems and biomedical applications based on NIR-II imaging, such as multimodal imaging, photothermal and photodynamic therapy, guidance for intraoperative surgery, and drug delivery.
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                Author and article information

                Journal
                Advanced Materials
                Adv. Mater.
                Wiley
                0935-9648
                1521-4095
                April 26 2019
                April 26 2019
                : 1900321
                Affiliations
                [1 ]Laboratory of Molecular Imaging and NanomedicineNational Institute of Biomedical Imaging and Bioengineering (NIBIB)National Institutes of Health (NIH) Bethesda MD 20892 USA
                [2 ]Department of ChemistryStanford University Stanford CA 94305 USA
                Article
                10.1002/adma.201900321
                6555689
                31025403
                e2faee07-dbb8-4753-af79-548fc503d2ae
                © 2019

                http://doi.wiley.com/10.1002/tdm_license_1.1

                History

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