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Self-assembled nanostructured photosensitizer with aggregation-induced emission for enhanced photodynamic anticancer therapy

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  • ReceivedJun 15, 2019
  • AcceptedJul 22, 2019
  • PublishedAug 22, 2019

Abstract

Three nanostructured photosensitizers with aggregation-induced emission (AIE) characteristics based on 2,3-bis(4ʹ-(diphenylamino)-[1,1ʹ-biphenyl]-4-yl) fumaronitrile (BDBF) were prepared for image-guided photodynamic therapy (PDT). BDBF was encapsulated with Pluronic F-127 (F127) to form usual spherical nanoparticles (F127@BDBF NPs) with a red fluorescence emission and 9.8% fluorescence quantum yield (FQY). Moreover, BDBF self-assembled into nanorods (BDBF NRs) in water. Compared with F127@BDBF NPs, BDBF NRs exhibited stronger orange fluorescence with a higher FQY of 23.3% and similar singlet oxygen (1O2) generation capability. BDBF NRs were further modified with F127 to form BDBF@F127 NRs with the same 1O2 generation ability as BDBF NRs. The three nanostructures exhibited a higher 1O2 production capacity than BDBF molecule in dissolved state and favorable stability in an aqueous solution as well as under physiological condition. In vitro photocytotoxicity experiments indicated that the three nanostructures inhibited tumor cell proliferation effectively. Therefore, to construct eligible nanostructures with a high FQY and 1O2 generation ability, simple self-assembly can serve as a valuable method to prepare photosensitizers with enhanced PDT.


Funded by

the Natural Science Foundation of China(21835001,51773080,21674041,51573068,21221063,81870117)

Program for Changbaishan Scholars of Jilin Province

Jilin Province project(20160101305JC)

the Jilin Province Science and Technology Development Plan(20190201252JC)

and the “Talents Cultivation Program” of Jilin University.


Acknowledgment

This work was financially supported by the National Natural Science Foundation of China (21835001, 51773080, 21674041, 51573068, 21221063, and 81870117), the Program for Changbaishan Scholars of Jilin Province, Jilin Province project (20160101305JC), Jilin Province Science and Technology Development Plan (20190201252JC), and “Talents Cultivation Program” of Jilin University.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Han W designed and performed the experiments, analyzed data and wrote the paper; Zhang S, Deng R, Qian J and Zheng X performed partial experiments. Yan F designed partial experiments. Tian W conceived the framework of this paper and revised the paper. All authors contributed to the general discussion.


Author information

Wenkun Han received his BSc degree from Jilin University (JLU) in 2015. He is currently a PhD candidate under the supervision of Prof. Wenjing Tian. His research interest focuses on the self-assembly fluorogens for bioimaging and anticancer applications.


Fei Yan is an associate professor in the Chemistry Department, JLU. He received his PhD degree from JLU in 2010, and worked as a postdoctoral fellow first at Ohio State University and then at the University of Minnesota during 2010–2017. His research interests include the bioinorganic chemistry, translational nanomedicine and cancer epigenetics.


Wenjing Tian received her Bachelor’s degree from the Department of Physics, JLU in 1988, and her PhD from Changchun Institute of Applied Chemistry, Chinese Academy of Sciences in 1993. She was a postdoctoral fellow at the Department of Chemistry, JLU from 1994 to 1996. She is currently a professor at the State Key Laboratory of Supramolecular Structure and Materials of JLU. Her research interest focuses on organic/polymer optoelectronic materials and devices.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


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  • Figure 1

    Average sizes of (a) BDBF NRs, (b) BDBF@F127 NRs, and (c) F127@BDBF NPs detected by DLS (inset: TEM images of the corresponding NPs, scale bar: 200 nm). Normalized absorbance and fluorescence spectra of (d) BDBF NRs, (e) BDBF@F127 NRs, and (f) F127@BDBF NPs.

  • Scheme 1

    Schematic of BDBF NRs and F127@BDBF NPs AIEgen PSs nanostructures for image-guided PDT.

  • Figure 2

    AIE properties of BDBF in DMF with different water fractions.

  • Figure 3

    Photostability of ICG in water (a, e, i) and in DMF (m) under light irradiation in the absence of any PS; the absorbance of ICG with the same concentrations of BDBF NRs (b), BDBF@F127 NRs (f), F127@BDBF NPs (j), and BDBF in DMF (n) without light irradiation (BDBF: 30 μmol L−1); UV-vis absorption spectra changes in the 1O2 indicator ICG mixed with BDBF NRs (c), BDBF@F127 NRs (g), F127@BDBF NPs (k), and BDBF in DMF (o) for different durations of light irradiation; the quantification of 1O2 generation capability with the decrease in absorbance at 790 nm for BDBF NRs (d), BDBF@F127 NRs (h), F127@BDBF NPs (l), and BDBF in DMF (p) under light irradiation (12  mW cm−2).

  • Figure 4

    CLSM of A549 cells incubated with BDBF NRs, BDBF@F127 NRs, and F127@BDBF NPs for 4 h at 37°C (BDBF: 5 μmol L−1). For each panel, the images from left to right show the cell nuclei stained with Hoechst 33258 (blue), BDBF NRs (a), BDBF@F127 NRs (b), and F127@BDBF NPs (c) fluorescence in cells (orange or red), and overlays of both images. Scale bar: 20 μm.

  • Figure 5

    In vitro dark and phototoxicities of BDBF NRs (a), BDBF@F127 NRs (b), and F127@BDBF NPs (c) against A549 cells at different concentrations of BDBF (0–60 μmol L−1) with an LED lamp at a power density of 12 mW cm−2 for 60 min.

  • Table 1   Average size, zeta potential, PDI, and FQY of three nanostructures

    BDBF NRs

    BDBF@F127 NRs

    F127@BDBF NPs

    Size (nm)

    179.2

    207.0

    72.6

    Zeta (mV)

    −44.8

    −20.4

    −7.69

    PDI

    0.084

    0.097

    0.216

    FDY (%)

    23.3

    21.9

    9.8

    τave (ns)

    3.67

    2.89

    4.75

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