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Engineering molecular self-assembly of theranostic nanoprobes for dual-modal imaging-guided precise chemotherapy

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  • ReceivedFeb 1, 2021
  • AcceptedFeb 24, 2021
  • PublishedMar 19, 2021

Abstract


Funded by

the National Natural Science Foundation of China(21878087,21908060)

the Innovation Program of Shanghai Municipal Education Commission

Shuguang Program(18SG27)

was approved by the Institutional Animal Care and Use Committee of National Tissue Engineering Center(Shanghai,China)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21878087, 21908060), the Innovation Program of Shanghai Municipal Education Commission, Shuguang Program (18SG27). This study was performed in strict accordance with the NIH guidelines for the care and use of laboratory animals (NIH Publication No. 85-23 Rev. 1985) and was approved by the Institutional Animal Care and Use Committee of National Tissue Engineering Center (Shanghai, China).


Interest statement

The authors declare no conflict of interest.


Supplement

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Scheme 1

    Molecularly precise self-assembling nanotheranostic BPn-Cy-S-CPT (n=0, 5, and 20). BP20-Cy-S-CPT synergistically unites dual-modal photoacoustic/NIR fuorescence imaging for precise diagnosis and chemotherapy: PA signals provide the in vivo delivery profile with high spatial resolution; distinct dual-channel NIR fluorescence (815 and 660 nm) performs real-timely tracking in vivo behaviors of before and after prodrug-activation without blind spot (color online).

  • Figure 1

    Amphiphilic self-assembly of BP20-Cy-S-CPT with synergistically enhanced fluorescence & PA signals. (a) Size distribution and (b) TEM image. (c) BP20-Cy-S-CPT self-assemblies display high stable in aqueous solution (PBS, pH 7.4) over 5 days. (d) CMC analysis of BP20-Cy-S-CPT by using pyrene as a fluorescent indicator. Fluorescence intensity at 815 nm (e) and 660 nm (f) of BP20-Cy-S-CPT self-assemblies in fresh human serum over 24 h at 37 °C. Fluorescence intensity at 815 nm (g) and 660 nm (h) of BP20-Cy-S-CPT as a function of pH value at 37 °C. (i) The fluorescence intensity of BPn-Cy-S-CPT (n=0, 5, 20) at 815 nm in aqueous solution (PBS, pH 7.4). (j) Emission spectrum of BP20-Cy-S-CPT in aqueous solution (PBS, pH 7.4). (k) The PA signal intensity (at 800 nm) of BPn-Cy-S-CPT in aqueous solution (PBS, pH 7.4). (l) PA spectrum of BP20-Cy-S-CPT in aqueous solution (PBS, pH 7.4). Note: Data are shown as mean ± s.d., with n=3 (color online).

  • Figure 2

    GSH-triggered dual-channel fluorescence response and concomitant active drug release. Absorbption (a) and emission spectra ((b) λex=730 nm; (c) λex=550 nm) of BP20-Cy-S-CPT (10 μM) with the presence of GSH in aqueous solution (PBS, pH 7.4, 37 °C). Time-dependent fluorescence response at 815 nm (d) and 660 nm (e) for BP20-Cy-S-CPT with the addition of GSH (2.5 mM) in aqueous solution (PBS, pH 7.4, 37 °C). Inset: HPLC analysis for evaluating the CPT release from BP20-Cy-S-CPT. (f) Selectivity test for BP20-Cy-S-CPT toward GSH. Inset: images of BP20-Cy-S-CPT with GSH and other amino acids under white (up) and ultraviolet (UV) light (down) irridation. Note: Data are shown as mean ± s.d., with n=3 (color online).

  • Figure 3

    Assembling and active targeting effect on in vitro cytotoxicity and cellular internalization. 3T3 (a) and HeLa cells (b) were incubated with BPn-Cy-S-CPT for 24 h. Dual-channel flow cytometry analysis of cellular internalization and GSH-induced activation of BP20-Cy-S-CPT in 3T3 cells ((c) λem=815 nm; (e) λem=660 nm) and HeLa cells ((d) λem=815 nm; (f) λem=660 nm). Note: Data are shown as mean ± s.d., with n=3 (color online).

  • Figure 4

    Distribution and activation of BP20-Cy-S-CPT in normal and cancer cells. Csll images of BP20-Cy-S-CPT in 3T3 cells (a), HeLa cells (b) and A549 cells (c). Channel 0: bright field; Channel 1: nucleus was stained with DAPI; Channel 2: 815 nm NIR channel; Channel 3: 660 nm NIR channel; Channel 4: overlapped field (color online).

  • Figure 5

    In vivo dual-modal PA/fluorescence imaging of BP20-Cy-S-CPT. (a) After intravenous injection, we recorded the PA imaging of BP20-Cy-S-CPT in artificial prosthesis, and the mice bearing subcutaneous HeLa-tumor xenografts. (b) Schematic illustration of the synergistic targeting (passive, active, and activatable targeting) of BP20-Cy-S-CPT. (c) In vivo dual-channel NIR fluorescence imaging at 815 nm (yellow-red scale) and 660 nm (rainbow scale) after intravenous injection of BP20-Cy-S-CPT. Dual-channel NIR fluorescence imaging of excised organs at 24 h after the intravenous injection (color online).

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