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Nano Research 2019, 12(5): 999-1008 https://doi.org/10.1007/s12274-019-2330-y
Research Article | Open Access | Issue | Published: 06 March 2019

Photodynamic therapy-triggered on-demand drug release from ROS-responsive core-cross-linked micelles toward synergistic anti-cancer treatment

Show Author's Information Yongjuan Li1,  Jian Hu2,  Xun Liu1,  Yong Liu3( ),  Shixian Lv1,  Juanjuan Dang1,  Yong Ji4( ),  Jinlin He2,  Lichen Yin1( )
Institute of Functional Nano and Soft Materials (FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University,Suzhou,215123,China;
College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,Soochow University,Suzhou,215123,China;
Department of Biomedical Engineering,University of Groningen and University Medical Center Groningen,Antonius Deusinglaan, 1, 9713 AV Groningen,The Netherlands;
Department of Cardiothoracic Surgery,Wuxi People's Hospital Affiliated to Nanjing Medical University,Wuxi,214023,China;
Keywords:
photodynamic therapy, core-cross-linked micelles, on-demand drug release, reactive oxygen species (ROS) responsiveness, synergistic anti-cancer therapy
Topics:
Controlled drug deliveryDiseasesMicelles Targeted drug delivery
Cite this article:
Li Y, Hu J, Liu X, et al. Photodynamic therapy-triggered on-demand drug release from ROS-responsive core-cross-linked micelles toward synergistic anti-cancer treatment. Nano Research, 2019, 12(5): 999-1008. https://doi.org/10.1007/s12274-019-2330-y
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Abstract Full text Electronic supplementary material About this article

Polymeric micelles have demonstrated wide utility for chemodrug delivery, which however, still suffer from shortcomings such as undesired drug loading, disassembly upon dilution, pre-leakage of drug cargoes during systemic circulation, and lack of cancer-selective drug release. Herein, a poly(ethylene glycol) (PEG)-polyphosphoester-based, reactive oxygen species (ROS)-responsive, core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin, Dox) and photosensitizer (chlorin e6, Ce6). The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker, which notably enhanced the drug loading and micelle stability. In tumor cells, far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores. As such, micelles were destabilized and Dox release was promoted, which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy. This study provides an effective approach to realize the precise control over drug loading, formulation stability, and cancer-selective drug release using polymeric micelles, and would render promising utilities for the programmed anti-cancer combination therapy.


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Electronic supplementary material
About this article

Photodynamic therapy-triggered on-demand drug release from ROS-responsive core-cross-linked micelles toward synergistic anti-cancer treatment

Show Author's information Yongjuan Li1, Jian Hu2, Xun Liu1, Yong Liu3( ), Shixian Lv1, Juanjuan Dang1, Yong Ji4( ), Jinlin He2, Lichen Yin1( )
Institute of Functional Nano and Soft Materials (FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University,Suzhou,215123,China;
College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,Soochow University,Suzhou,215123,China;
Department of Biomedical Engineering,University of Groningen and University Medical Center Groningen,Antonius Deusinglaan, 1, 9713 AV Groningen,The Netherlands;
Department of Cardiothoracic Surgery,Wuxi People's Hospital Affiliated to Nanjing Medical University,Wuxi,214023,China;

Abstract

Polymeric micelles have demonstrated wide utility for chemodrug delivery, which however, still suffer from shortcomings such as undesired drug loading, disassembly upon dilution, pre-leakage of drug cargoes during systemic circulation, and lack of cancer-selective drug release. Herein, a poly(ethylene glycol) (PEG)-polyphosphoester-based, reactive oxygen species (ROS)-responsive, core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin, Dox) and photosensitizer (chlorin e6, Ce6). The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker, which notably enhanced the drug loading and micelle stability. In tumor cells, far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores. As such, micelles were destabilized and Dox release was promoted, which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy. This study provides an effective approach to realize the precise control over drug loading, formulation stability, and cancer-selective drug release using polymeric micelles, and would render promising utilities for the programmed anti-cancer combination therapy.

Keywords: photodynamic therapy, core-cross-linked micelles, on-demand drug release, reactive oxygen species (ROS) responsiveness, synergistic anti-cancer therapy

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Publication history

Received: 16 December 2018
Revised: 03 February 2019
Accepted: 04 February 2019
Published: 06 March 2019
Issue date: May 2019

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© The Author(s) 2019

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 51722305, 51573123, and 51873142), the Ministry of Science and Technology of China (No. 2016YFA0201200), the 111 Project, and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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