Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)- g -Chitosan Copolymer
Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan...
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| Veröffentlicht in: | International journal of molecular sciences 2021-12, Vol.22 (23), p.13169 |
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| creator | Yoon, Hyun-Min Kang, Min-Su Choi, Go-Eun Kim, Young-Joon Bae, Chang-Hyu Yu, Young-Bob Jeong, Young-Il |
| description | Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties. |
| doi_str_mv | 10.3390/ijms222313169 |
| format | Article |
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We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222313169</identifier><identifier>PMID: 34884973</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antibiotics, Antineoplastic - chemistry ; Antibiotics, Antineoplastic - pharmacology ; Apoptosis ; Backbone ; Cancer therapies ; Cell culture ; Cell Proliferation ; Chitosan ; Chitosan - analogs & derivatives ; Chitosan - chemistry ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Copolymers ; Doxorubicin ; Doxorubicin - chemistry ; Doxorubicin - pharmacology ; Drug delivery ; Drug delivery systems ; Drug Liberation ; Enzymes ; Glutathione - chemistry ; Humans ; Image transmission ; Internalization ; Iron oxides ; Magnetic fields ; Magnetite Nanoparticles - administration & dosage ; Magnetite Nanoparticles - chemistry ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanocomposites ; Nanoparticles ; Physiology ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Polymers - chemistry ; Sensitivity ; Therapeutic targets ; Tumor Cells, Cultured ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>International journal of molecular sciences, 2021-12, Vol.22 (23), p.13169</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - chemistry</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Apoptosis</subject><subject>Backbone</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell Proliferation</subject><subject>Chitosan</subject><subject>Chitosan - analogs & derivatives</subject><subject>Chitosan - chemistry</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Copolymers</subject><subject>Doxorubicin</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug Liberation</subject><subject>Enzymes</subject><subject>Glutathione - 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We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. 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| subjects | Animals Antibiotics, Antineoplastic - chemistry Antibiotics, Antineoplastic - pharmacology Apoptosis Backbone Cancer therapies Cell culture Cell Proliferation Chitosan Chitosan - analogs & derivatives Chitosan - chemistry Colonic Neoplasms - drug therapy Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Copolymers Doxorubicin Doxorubicin - chemistry Doxorubicin - pharmacology Drug delivery Drug delivery systems Drug Liberation Enzymes Glutathione - chemistry Humans Image transmission Internalization Iron oxides Magnetic fields Magnetite Nanoparticles - administration & dosage Magnetite Nanoparticles - chemistry Male Mice Mice, Inbred BALB C Mice, Nude Nanocomposites Nanoparticles Physiology Polyethylene glycol Polyethylene Glycols - chemistry Polymers - chemistry Sensitivity Therapeutic targets Tumor Cells, Cultured Tumors Xenograft Model Antitumor Assays |
| title | Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)- g -Chitosan Copolymer |
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