Reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate- co -dithiolane trimethylene carbonate) micelles: Synthesis and CD44-mediated potent delivery of docetaxel to triple negative breast tumor in vivo

Yaqin Zhu, Jian Zhang, Fenghua Meng, Liang Cheng (Corresponding Author), Jan Feijen (Corresponding Author), Zhiyuan Zhong (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Future cancer therapy relies on the development of simple, selective and bioresponsive nanomedicines. Herein, we report that reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles (HA-CCMs) can be easily synthesized and achieve efficient CD44-mediated delivery and triggered cytoplasmic release of docetaxel (DTX) to MDA-MB-231 human triple negative breast tumor in vivo. DTX-loaded HA-CCMs exhibited a favorable size of 85 nm, low drug leakage and glutathione-responsive DTX release. HA-CCMs were efficiently taken up by CD44-overexpressing MDA-MB-231 cells as indicated by flow cytometry. DTX-loaded HA-CCMs induced selective apoptotic activity toward MDA-MB-231 cells in vitro. Notably, over 7-fold longer blood circulation time and 4-fold stronger tumor accumulation were observed for DTX-loaded HA-CCMs compared to free DTX. Cy5-labeled HA-CCMs revealed deep tumor penetration at 6 h post injection. DTX-loaded HA-CCMs were shown to effectively suppress the progression of MDA-MB-231 tumor and significantly extend mice survival time. These hyaluronic acid-shelled and disulfide-crosslinked micelles with great simplicity and selectivity are highly promising for treating various CD44-overexpressing cancers.

Original languageEnglish
Pages (from-to)3040-3047
Number of pages8
JournalJournal of Materials Chemistry B
Volume6
Issue number19
DOIs
Publication statusPublished - 1 Jan 2018

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docetaxel
Hyaluronic acid
Micelles
Hyaluronic Acid
Tumors
Carbonates
trimethylene carbonate
polytrimethylene carbonate

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@article{566cbb2577714e6e9a0e6913fdeaa77f,
title = "Reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate- co -dithiolane trimethylene carbonate) micelles: Synthesis and CD44-mediated potent delivery of docetaxel to triple negative breast tumor in vivo",
abstract = "Future cancer therapy relies on the development of simple, selective and bioresponsive nanomedicines. Herein, we report that reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles (HA-CCMs) can be easily synthesized and achieve efficient CD44-mediated delivery and triggered cytoplasmic release of docetaxel (DTX) to MDA-MB-231 human triple negative breast tumor in vivo. DTX-loaded HA-CCMs exhibited a favorable size of 85 nm, low drug leakage and glutathione-responsive DTX release. HA-CCMs were efficiently taken up by CD44-overexpressing MDA-MB-231 cells as indicated by flow cytometry. DTX-loaded HA-CCMs induced selective apoptotic activity toward MDA-MB-231 cells in vitro. Notably, over 7-fold longer blood circulation time and 4-fold stronger tumor accumulation were observed for DTX-loaded HA-CCMs compared to free DTX. Cy5-labeled HA-CCMs revealed deep tumor penetration at 6 h post injection. DTX-loaded HA-CCMs were shown to effectively suppress the progression of MDA-MB-231 tumor and significantly extend mice survival time. These hyaluronic acid-shelled and disulfide-crosslinked micelles with great simplicity and selectivity are highly promising for treating various CD44-overexpressing cancers.",
author = "Yaqin Zhu and Jian Zhang and Fenghua Meng and Liang Cheng and Jan Feijen and Zhiyuan Zhong",
year = "2018",
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Reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate- co -dithiolane trimethylene carbonate) micelles : Synthesis and CD44-mediated potent delivery of docetaxel to triple negative breast tumor in vivo. / Zhu, Yaqin; Zhang, Jian; Meng, Fenghua; Cheng, Liang (Corresponding Author); Feijen, Jan (Corresponding Author); Zhong, Zhiyuan (Corresponding Author).

In: Journal of Materials Chemistry B, Vol. 6, No. 19, 01.01.2018, p. 3040-3047.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate- co -dithiolane trimethylene carbonate) micelles

T2 - Synthesis and CD44-mediated potent delivery of docetaxel to triple negative breast tumor in vivo

AU - Zhu, Yaqin

AU - Zhang, Jian

AU - Meng, Fenghua

AU - Cheng, Liang

AU - Feijen, Jan

AU - Zhong, Zhiyuan

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Future cancer therapy relies on the development of simple, selective and bioresponsive nanomedicines. Herein, we report that reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles (HA-CCMs) can be easily synthesized and achieve efficient CD44-mediated delivery and triggered cytoplasmic release of docetaxel (DTX) to MDA-MB-231 human triple negative breast tumor in vivo. DTX-loaded HA-CCMs exhibited a favorable size of 85 nm, low drug leakage and glutathione-responsive DTX release. HA-CCMs were efficiently taken up by CD44-overexpressing MDA-MB-231 cells as indicated by flow cytometry. DTX-loaded HA-CCMs induced selective apoptotic activity toward MDA-MB-231 cells in vitro. Notably, over 7-fold longer blood circulation time and 4-fold stronger tumor accumulation were observed for DTX-loaded HA-CCMs compared to free DTX. Cy5-labeled HA-CCMs revealed deep tumor penetration at 6 h post injection. DTX-loaded HA-CCMs were shown to effectively suppress the progression of MDA-MB-231 tumor and significantly extend mice survival time. These hyaluronic acid-shelled and disulfide-crosslinked micelles with great simplicity and selectivity are highly promising for treating various CD44-overexpressing cancers.

AB - Future cancer therapy relies on the development of simple, selective and bioresponsive nanomedicines. Herein, we report that reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles (HA-CCMs) can be easily synthesized and achieve efficient CD44-mediated delivery and triggered cytoplasmic release of docetaxel (DTX) to MDA-MB-231 human triple negative breast tumor in vivo. DTX-loaded HA-CCMs exhibited a favorable size of 85 nm, low drug leakage and glutathione-responsive DTX release. HA-CCMs were efficiently taken up by CD44-overexpressing MDA-MB-231 cells as indicated by flow cytometry. DTX-loaded HA-CCMs induced selective apoptotic activity toward MDA-MB-231 cells in vitro. Notably, over 7-fold longer blood circulation time and 4-fold stronger tumor accumulation were observed for DTX-loaded HA-CCMs compared to free DTX. Cy5-labeled HA-CCMs revealed deep tumor penetration at 6 h post injection. DTX-loaded HA-CCMs were shown to effectively suppress the progression of MDA-MB-231 tumor and significantly extend mice survival time. These hyaluronic acid-shelled and disulfide-crosslinked micelles with great simplicity and selectivity are highly promising for treating various CD44-overexpressing cancers.

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U2 - 10.1039/c8tb00094h

DO - 10.1039/c8tb00094h

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JO - Journal of materials chemistry. B: materials for biology and medicine

JF - Journal of materials chemistry. B: materials for biology and medicine

SN - 2050-750X

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