Simple Preparation of Near-infrared-II Organic Small Molecule-based Phototheranostics by Manipulation of the Electron-donating Unit

doi:10.6023/A22060267

Abstract

Organic small molecules hold great promise in the field of phototheranostics by virtue of their clear chemical structure, outstanding biocompatibility, and distinguished repeatability. Whereas the synthetic process of them suffers from multi-step and complex reactions. Meanwhile, most of small molecules employed near-infrared-I (NIR-I) fluorescence imaging, which could not effectively provide comprehensive tumor information with high resolution. In addition, the reported small molecules showed unsatisfactory singlet oxygen yield and photothermal conversion eﬃciency, limiting their extensive application in cancer theranostics. Herein, by conjugating diketopyrrolopyrrole (an electron-withdrawing unit) with benzene, aniline, or 1,2-diaminobenzene (electron-donating units), respectively, three novel small molecules DPP-0, DPP-2 and DPP-4 were designed and synthesized by one-step reaction. DPP-0 NPs, DPP-2 NPs and DPP-4 NPs as phototheranostics were further obtained through nanoprecipitation method by self-assembling with Pluronic F127. It was found that with the increase of amino groups, the absorption/emission peaks of NPs were red-shifted. Especially, DPP-4 NPs exhibited strong absorption in the NIR-I region, and the maximum emission peak of DPP-4 NPs was located in the near-infrared-II (NIR-II) region, suggesting that the optical properties of small molecules can be regulated by changing the electron-donating unit. After irradiation of DPP-4 NPs with a single laser, excellent NIR-II fluorescence signal can be obtained for efficient imaging of tumor with high resolution. Moreover, abundant reactive oxygen species (singlet oxygen yield 34.3%) and hyperthermia (photothermal conversion efficiency 40.2%) can also be produced by irradiation of DPP-4 NPs, realizing the combined photodynamic/photothermal therapy guided by NIR-II fluorescence imaging.

Key words: organic small molecule, phototheranostics, near-infrared-II fluorescence imaging, photodynamic therapy, photothermal therapy

Cite this article

Qi Wang, Hui Xia, Yanwei Xiong, Xinmin Zhang, Jie Cai, Chong Chen, Yicong Gao, Feng Lu, Quli Fan. Simple Preparation of Near-infrared-II Organic Small Molecule-based Phototheranostics by Manipulation of the Electron-donating Unit[J]. Acta Chimica Sinica, 2022, 80(11): 1485-1493.

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Fig. & Tab. 7

Figure 1. (a) Chemical structures of DPP-0, DPP-2 and DPP-4, as well as schematic illustration of nanoparticles; (b) schematic illustration of DPP-4 NPs for phototheranostics

Figure 2. (a) Absorption and (b) fluorescence emission spectra of DPP-0, DPP-2 and DPP-4 in THF; (c) absorption and (d) fluorescence emission spectra of DPP-0 NPs, DPP-2 NPs and DPP-4 NPs in water; (e) DLS and TEM data of DPP-4 NPs, scale bar: 100 nm; (f) stability of DPP-4 NPs

Figure 3. (a) The heating curves of DPP-4 NPs under laser irradiation with different power densities; (b) the heating curves of DPP-4 NPs at different concentrations under laser irradiation with the same power density; (c) infrared thermal images of DPP-4 NPs at various concentrations under laser irradiation; (d) photothermal stability of DPP-4 NPs

Figure 4. Absorption spectra of mixed aqueous solutions of DPP-4 NPs and DPBF under 660 nm laser irradiation at different power densities: (a) 0.5 W?cm?2, (b) 0.75 W?cm?2, (c) 1.0 W?cm?2; (d) the intensity changes of the absorption peak of DPBF under laser irradiation with different power densities; (e) the detection of ROS in Hela cells

Figure 5. (a) Confocal images of Hela cells incubated with FITC NPs for 6 h and 12 h; (b) flow cytometric analysis of fluorescence intensity of Hela cells incubated with FITC NPs for 6 h and 12 h; (c) determination of the biosafety of DPP-4 NPs against NIH3T3 normal cells; (d) determination of the phototoxicity of DPP-4 NPs to Hela cells; (e) live/dead cell staining analysis

Figure 6. (a) NIR-II intensity of DPP-4 NPs at different concentrations; (b) NIR-II images of DPP-4 NPs after covered chicken-breast tissue; (c) NIR-II imaging of Hela-tumor-bearing mice after injection of DPP-4 NPs; (d) NIR-II signal intensities of the tumor site at different post-injection times

Figure 7. (a) Relative tumor volume changes of mice during therapy; (b) tumor weight changes of mice after therapy; (c) body weight changes of mice during therapy; (d) H&E staining of major organs after therapy, scale bars: 100 μm

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