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

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(ethyle...

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Published in	Nano research Vol. 12; no. 5; pp. 999 - 1008
Main Authors	Li, Yongjuan, Hu, Jian, Liu, Xun, Liu, Yong, Lv, Shixian, Dang, Juanjuan, Ji, Yong, He, Jinlin, Yin, Lichen
Format	Journal Article
Language	English
Published	Beijing Tsinghua University Press 01.05.2019 Springer Nature B.V
Subjects	Anticancer properties Atomic/Molecular Structure and Spectra Biomedicine Biotechnology Cancer Cancer therapies Chemistry and Materials Science Condensed Matter Physics Control stability Crosslinking Dilution Dismantling Doxorubicin Drug delivery systems Hydrophobicity Irradiation Light irradiation Materials Science Micelles Nanotechnology Photodynamic therapy Polyethylene glycol Radiation Reactive oxygen species Research Article Tumor cells Utilities on-demand drug release core-cross-linked micelles photodynamic therapy synergistic anti-cancer therapy reactive oxygen species (ROS) responsiveness
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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.
AbstractList	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.
Author	Lv, Shixian Dang, Juanjuan Hu, Jian Ji, Yong He, Jinlin Yin, Lichen Liu, Yong Li, Yongjuan Liu, Xun
Author_xml	– sequence: 1 givenname: Yongjuan surname: Li fullname: Li, Yongjuan organization: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University – sequence: 2 givenname: Jian surname: Hu fullname: Hu, Jian organization: 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 – sequence: 3 givenname: Xun surname: Liu fullname: Liu, Xun organization: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University – sequence: 4 givenname: Yong surname: Liu fullname: Liu, Yong email: y.liu@umcg.nl organization: Department of Biomedical Engineering, University of Groningen and University Medical Center Groningen – sequence: 5 givenname: Shixian surname: Lv fullname: Lv, Shixian organization: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University – sequence: 6 givenname: Juanjuan surname: Dang fullname: Dang, Juanjuan organization: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University – sequence: 7 givenname: Yong surname: Ji fullname: Ji, Yong email: jiyongmyp@163.com organization: Department of Cardiothoracic Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University – sequence: 8 givenname: Jinlin surname: He fullname: He, Jinlin organization: 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 – sequence: 9 givenname: Lichen surname: Yin fullname: Yin, Lichen email: lcyin@suda.edu.cn organization: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University
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Snippet	Polymeric micelles have demonstrated wide utility for chemodrug delivery, which however, still suffer from shortcomings such as undesired drug loading,...
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SubjectTerms	Anticancer properties Atomic/Molecular Structure and Spectra Biomedicine Biotechnology Cancer Cancer therapies Chemistry and Materials Science Condensed Matter Physics Control stability Crosslinking Dilution Dismantling Doxorubicin Drug delivery systems Hydrophobicity Irradiation Light irradiation Materials Science Micelles Nanotechnology Photodynamic therapy Polyethylene glycol Radiation Reactive oxygen species Research Article Tumor cells Utilities
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Title	Photodynamic therapy-triggered on-demand drug release from ROS-responsive core-cross-linked micelles toward synergistic anti-cancer treatment
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