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Synthesis, Characterization, and Biomedical Applications of a Targeted Dual-Modal Near-Infrared-II Fluorescence and Photoacoustic Imaging Nanoprobe

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Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, Stanford, California 94305-5344, United States
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305-5847, United States
§ School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044, China
Department of Ultrasound, Chinese Academy of Medical Science, Peking Union Medical College Hospital, Beijing 100730, China
Cite this: ACS Nano 2017, 11, 12, 12276–12291
Publication Date (Web):December 4, 2017
https://doi.org/10.1021/acsnano.7b05966
Copyright © 2017 American Chemical Society

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    Our development of multifunctional dual-modal imaging probes aims to integrate the benefits from both second near-infrared (NIR-II) fluorescence (1000–1700 nm) and photoacoustic imaging with an ultimate goal of improving overall cancer diagnosis efficacy. Herein we designed a donor–acceptor chromophore based nanoparticle (DAP) as a dual-modal image contrast agent has strong absorption in the NIR-I window and a strong fluorescence emission peak in the NIR-II region. The dual-modal DAPs composed of D−π–A−π–D-type chromophores were PEGylated through nanoprecipitation. The multifunctional DAP surface was thus available for subsequent bioconjugation of EGFR Affibody (Ac-Cys-ZEGFR:1907) to target EGFR-positive cancers. The Affibody-conjugated DAPs appeared as highly monodisperse nanoparticles (∼30 nm) with strong absorption in the NIR-I window (at ca. 680 nm) and an extremely high fluorescence in the NIR-II region (maximum peak at 1000 nm). Consequently, the Affibody–DAPs show significantly enhanced photoacoustic and NIR-II fluorescence contrast effects in both in vitro and in vivo experiments. Moreover, the Affibody–DAPs have the capability to selectively target EGFR-positive tumors in an FTC-133 subcutaneous mouse model with relatively high photoacoustic and fluorescent signals. By taking advantage of high spatial resolution and excellent temporal resolution, photoacoustic/NIR-II fluorescence imaging with targeted dual-modal contrast agents allows us to specifically image and detect various cancers and diseases in an accurate manner.

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