A hyperbranched amphiphilic acetal polymer for pH-sensitive drug delivery

Hongliang Cao; Chao Chen; Debiao Xie; Xin Chen; Ping Wang; Yibing Wang; Huajie Song; Wenxin Wang

doi:10.1039/c7py01739a

A hyperbranched amphiphilic acetal polymer for pH-sensitive drug delivery

Hongliang Cao, Chao Chen, Debiao Xie, Xin Chen, Ping Wang, Yibing Wang, Huajie Song, Wenxin Wang

Bioproducts and Biosystems Engineering

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Nanoparticles are appealing drug delivery systems since they promise prolonged circulation time and predictable release behaviors. The current work reports a novel hyperbranched amphiphilic block copolymer synthesized using deactivation-enhanced atom transfer radical polymerization (DE-ATRP) for smart drug delivery. PEG2000-Br was applied as a macroinitiator to initiate acid-cleavable divinyl (ACD) monomers linked by acetal groups, formulating the hydrophilic (PEG) and hydrophobic (ACD) segments. The polymer appeared to self-assemble into micelles with diameters in the range of 70-100 nm, and was examined for the controlled release of doxorubicin (DOX). Results showed that DOX-loaded micelles (∼90 nm) could achieve drug loading as high as 8.2 wt%, with interesting pH-dependent release behaviors. Studies with flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) showed that DOX-loaded micelles exhibited a high cellular uptake performance by HeLa cells, which indicated promising anti-tumor efficacy for such a drug delivery system. Additionally, such DOX-loaded micelles exhibited remarkable cytotoxicity against HeLa cells in a dose- and time-dependent manner due to the enhanced cell uptake behavior of micelles. These results indicated that the polymeric micelles might be used as a promising candidate for a pH-responsive drug delivery for cancer therapy.

Original language	English (US)
Pages (from-to)	169-177
Number of pages	9
Journal	Polymer Chemistry
Volume	9
Issue number	2
DOIs	https://doi.org/10.1039/c7py01739a
State	Published - Jan 14 2018

Bibliographical note

Funding Information:
This work was supported by the Shanghai Leading Academic Discipline Project (B502), the Shanghai Key Laboratory Project (08DZ2230500), the National Natural Science Foundation of China (21303050, 31471659 and 21636003), the Fundamental Research Funds for the Central Universities (222201514327), the State Key Laboratory of Functional Materials for Informatics Open Project (SKL201306) and the Shanghai Pujiang Program (13PJ1401700). Authors thank the support from the Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM).

Publisher Copyright:
© 2018 The Royal Society of Chemistry.

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title = "A hyperbranched amphiphilic acetal polymer for pH-sensitive drug delivery",

abstract = "Nanoparticles are appealing drug delivery systems since they promise prolonged circulation time and predictable release behaviors. The current work reports a novel hyperbranched amphiphilic block copolymer synthesized using deactivation-enhanced atom transfer radical polymerization (DE-ATRP) for smart drug delivery. PEG2000-Br was applied as a macroinitiator to initiate acid-cleavable divinyl (ACD) monomers linked by acetal groups, formulating the hydrophilic (PEG) and hydrophobic (ACD) segments. The polymer appeared to self-assemble into micelles with diameters in the range of 70-100 nm, and was examined for the controlled release of doxorubicin (DOX). Results showed that DOX-loaded micelles (∼90 nm) could achieve drug loading as high as 8.2 wt%, with interesting pH-dependent release behaviors. Studies with flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) showed that DOX-loaded micelles exhibited a high cellular uptake performance by HeLa cells, which indicated promising anti-tumor efficacy for such a drug delivery system. Additionally, such DOX-loaded micelles exhibited remarkable cytotoxicity against HeLa cells in a dose- and time-dependent manner due to the enhanced cell uptake behavior of micelles. These results indicated that the polymeric micelles might be used as a promising candidate for a pH-responsive drug delivery for cancer therapy.",

author = "Hongliang Cao and Chao Chen and Debiao Xie and Xin Chen and Ping Wang and Yibing Wang and Huajie Song and Wenxin Wang",

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AU - Cao, Hongliang

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AU - Chen, Xin

AU - Wang, Ping

AU - Wang, Yibing

AU - Song, Huajie

AU - Wang, Wenxin

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N2 - Nanoparticles are appealing drug delivery systems since they promise prolonged circulation time and predictable release behaviors. The current work reports a novel hyperbranched amphiphilic block copolymer synthesized using deactivation-enhanced atom transfer radical polymerization (DE-ATRP) for smart drug delivery. PEG2000-Br was applied as a macroinitiator to initiate acid-cleavable divinyl (ACD) monomers linked by acetal groups, formulating the hydrophilic (PEG) and hydrophobic (ACD) segments. The polymer appeared to self-assemble into micelles with diameters in the range of 70-100 nm, and was examined for the controlled release of doxorubicin (DOX). Results showed that DOX-loaded micelles (∼90 nm) could achieve drug loading as high as 8.2 wt%, with interesting pH-dependent release behaviors. Studies with flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) showed that DOX-loaded micelles exhibited a high cellular uptake performance by HeLa cells, which indicated promising anti-tumor efficacy for such a drug delivery system. Additionally, such DOX-loaded micelles exhibited remarkable cytotoxicity against HeLa cells in a dose- and time-dependent manner due to the enhanced cell uptake behavior of micelles. These results indicated that the polymeric micelles might be used as a promising candidate for a pH-responsive drug delivery for cancer therapy.

AB - Nanoparticles are appealing drug delivery systems since they promise prolonged circulation time and predictable release behaviors. The current work reports a novel hyperbranched amphiphilic block copolymer synthesized using deactivation-enhanced atom transfer radical polymerization (DE-ATRP) for smart drug delivery. PEG2000-Br was applied as a macroinitiator to initiate acid-cleavable divinyl (ACD) monomers linked by acetal groups, formulating the hydrophilic (PEG) and hydrophobic (ACD) segments. The polymer appeared to self-assemble into micelles with diameters in the range of 70-100 nm, and was examined for the controlled release of doxorubicin (DOX). Results showed that DOX-loaded micelles (∼90 nm) could achieve drug loading as high as 8.2 wt%, with interesting pH-dependent release behaviors. Studies with flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) showed that DOX-loaded micelles exhibited a high cellular uptake performance by HeLa cells, which indicated promising anti-tumor efficacy for such a drug delivery system. Additionally, such DOX-loaded micelles exhibited remarkable cytotoxicity against HeLa cells in a dose- and time-dependent manner due to the enhanced cell uptake behavior of micelles. These results indicated that the polymeric micelles might be used as a promising candidate for a pH-responsive drug delivery for cancer therapy.

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A hyperbranched amphiphilic acetal polymer for pH-sensitive drug delivery

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