Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of anticancer drugs

Changzhen Sun,Bin He,Chunhong Li,Ping Hao,Lu Qi,Na Hao,Zhirong Zhong,Jun Wang,Ji Lu,Lin Yang

doi:10.1186/s12951-020-00761-9

Changzhen Sun, Bin He + Show 8 more

Open Access

https://doi.org/10.1186/s12951-020-00761-9

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Abstract

BackgroundNano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject.ResultsTo construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells.ConclusionsA novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.

Highlights

Nano-drug delivery systems show considerable promise for effective cancer therapy
Considerable efforts on developing efficient polymeric micelles have been made in recent years, especially, several polymeric micelles have been reached to clinical trials [3, 4], the distribution of micelles and the release of the drug is difficult to trace in cancer cells [5, 6]
Scheme 2 Synthesis of the mPEG-ss-Tripp (I) and mPEG-Tripp (II) copolymer micelle opening and drug release, the count rate of the mPEG-ss-Tripp micelles decreased with time and with increasing GSH concentration (Fig. 4b). These results suggest that 10 mM GSH can trigger complete dissolution of mPEG-ss-Tripp micelles

Summary

Introduction

Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. The construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. The relevant AIE probes have been employed for cell imaging [18,19,20,21] This unique property makes the AIEactive polymeric micelles as the drug nanocarriers available for simultaneous cancer diagnostic and therapy. The GSH concentration in tumor cells is typically at least four times higher than the values of healthy cells [29, 30] In this context, the construction of a redox-sensitive multifunctional drug delivery system taking advantage of this characteristic for intelligent release of anticancer drugs and simultaneous cancer diagnostic and therapy remains an attractive research subject

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