Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle

Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (...

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Main Authors: Li, D., Tang, J., Chuan, W., Guo, J., Wang, S., Chaudhary, Deeptangshu, Wang, C.
Format: Journal Article
Published: Wiley - V C H Verlag GmbH & Co. KGaA 2012
Online Access:http://hdl.handle.net/20.500.11937/24931
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author Li, D.
Tang, J.
Chuan, W.
Guo, J.
Wang, S.
Chaudhary, Deeptangshu
Wang, C.
author_facet Li, D.
Tang, J.
Chuan, W.
Guo, J.
Wang, S.
Chaudhary, Deeptangshu
Wang, C.
author_sort Li, D.
building Curtin Institutional Repository
collection Online Access
description Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (–CONHNH2). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4–5 in the late stage of endolysosome and pH 5–6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release.
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institution Curtin University Malaysia
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publishDate 2012
publisher Wiley - V C H Verlag GmbH & Co. KGaA
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spelling curtin-20.500.11937-249312017-09-13T15:11:57Z Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle Li, D. Tang, J. Chuan, W. Guo, J. Wang, S. Chaudhary, Deeptangshu Wang, C. Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (–CONHNH2). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4–5 in the late stage of endolysosome and pH 5–6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release. 2012 Journal Article http://hdl.handle.net/20.500.11937/24931 10.1002/smll.201200272 Wiley - V C H Verlag GmbH & Co. KGaA restricted
spellingShingle Li, D.
Tang, J.
Chuan, W.
Guo, J.
Wang, S.
Chaudhary, Deeptangshu
Wang, C.
Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title_full Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title_fullStr Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title_full_unstemmed Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title_short Doxorubicin-Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle
title_sort doxorubicin-conjugated mesoporous magnetic colloidal nanocrystal clusters stabilized by polysaccharide as a smart anticancer drug vehicle
url http://hdl.handle.net/20.500.11937/24931