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A strategy for enhanced tumor targeting of photodynamic therapy based on Escherichiacoli-driven drug delivery system

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  • ReceivedFeb 25, 2020
  • AcceptedApr 18, 2020
  • PublishedJul 9, 2020

Abstract


Funding

the National Natural Science Foundation of China(81572944,21471033,21877113,81971983)

the CAS/SAFEA International Partnership Program for Creative Research Teams

and the FJIRSM&IUE Joint Research Fund(RHZX-2018-004)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (81572944, 21471033, 21877113 and 81971983), the CAS/SAFEA International Partnership Program for Creative Research Teams, the High-Level Entrepreneurship and Innovation Talents Projects in Fujian Province (2018-8-1), and the FJIRSM&IUE Joint Research Fund (RHZX-2018-004).


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Dai T and Chen Z conceived and designed the project. Ye F, Hu P and Chen J designed and synthesized zinc phthalo-cyanine conjugates 15. Dai T and Wang H performed the experiments. Dai T, Zhang L and Pan X analyzed the data. Chen J, Huang Y, Pan X and Huang M provided the technical support. Chen Z and Dai T finished the writing.


Author information

Tao Dai received his BSc degree in biotechnology from Anhui Normal University in 2014. Currently he is a Master student in Prof. Zhuo Chen’s group at Fujian Institute of Research on the Structure of Matter (FJIRSM), Chinese Academy of Sciences. His current research focuses on the targeted drug delivery in tumor therapy.


Zhuo Chen received her PhD from FJIRSM, Chinese Academy of Sciences, following her MD degree from Fujian Medical University and her BSc degree from Chinese Pharmaceutical University. From 2001 to 2008, she worked on molecular pharmacology & therapeutics in Loyola University Chicago as a Research Associate. Her research focuses on tumor detection and targeted photodynamic therapy, including design and synthesis of new anti-cancer drug entities and evaluation of their pharmacological effects through experiments in cells and animals.


Supplementary data

Supplementary information

Experimental details and supporting data are available in the online version of the paper.


References

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  • Figure 1

    Structural schematic diagram of ZnPc conjugates 1–7.

  • Figure 2

    Loading capacities of ZnPc conjugates 17 (10 µmol L−1) on E. coli. CLSM (a) and flow cytometer (b) results of fluorescence intensity of ZnPc conjugates 17 after incubation with E. coli. (c) Similar fluorescence intensity (relative fluorescence units, RFU) of ZnPc conjugates 17 (10 µmol L−1) and (d) the dose-dependent fluorescence intensity of E. coli after incubation with ZnPc-IR710. (e) The toxicity of ZnPc-IR710 (10 µmol L−1) for E. coli in dark.

  • Figure 3

    Phototoxicity of E. coli@ZnPc-IR710 against MCF-7 cells. (a) Flow cytometry analysis of MCF-7 cells after incubation with E. coli@ZnPc-IR710 (100 nmol L−1) and ZnPc-IR710 (100 nmol L−1), respectively. (b) Quantitatively analysis of the cellular uptake. (c) Dose-dependent phototoxicity of E. coli@ZnPc-IR710 against MCF-7 cells under 9 J cm−2 irradiation. (d) Analysis of cell cycle and apoptosis of MCF-7 cells after incubation with E. coli@ZnPc-IR710 (100 nmol L−1) or ZnPc-IR710 (100 nmol L−1), respectively. Significant difference is indicated by * and ** (at p<0.05 and at p<0.01, respectively) from the respective ZnPc-IR710-treated groups.

  • Figure 4

    Antitumor effect of E. coli@ZnPc-IR710 on 4T1-bearing mice. Relative tumor volume (a) and body weight (b) of 4T1 tumor-bearing mice. (c) Histological sections of important organs (heart, liver, kidney, spleen and lung) and tumor tissues from 4T1-bearing mice after the treatment with E. coli@ZnPc-IR710 (100×). The symbol * indicates a significant difference (at p<0.05) from the respective ZnPc-IR710-treated controls; # indicates a significant difference (at p<0.01) from the respective saline-treated controls.

  • Figure 5

    Pharmacokinetic study of E. coli@ZnPc-IR710 in 4T1 tumor-bearing mice. (a) Schematic diagram of the FMT imaging system. Determination of the concentration of ZnPc-IR710 in 4T1 tumor-bearing mice (b) and representative FMT images (c) at different time points after administration of E. coli@ZnPc-IR710 and ZnPc-IR710, respectively. Significant difference is indicated by * and ** (at p<0.05 and p<0.01, respectively) from the respective ZnPc-IR710-treated controls.

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