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 inNano 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
LanguageEnglish
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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Summary: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.
ISSN:1998-0124
1998-0000
DOI:10.1007/s12274-019-2330-y