Development of zwitterionic polymer-based doxorubicin conjugates : tuning the surface charge to prolong the circulation and reduce toxicity

Polymer-drug conjugates are commonly used as nano drug vehicles (NDVs) to delivery anticancer drugs. Zwitterionic polymers are ideal candidates to conjugate drugs because they show higher resistance to nonspecific protein adsorption in complex media than that of nonionic water-soluble polymers, such...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 30(2014), 13 vom: 08. Apr., Seite 3764-74
1. Verfasser: Wang, Zhen (VerfasserIn)
Weitere Verfasser: Ma, Guanglong, Zhang, Juan, Lin, Weifeng, Ji, Fangqin, Bernards, Matthew T, Chen, Shengfu
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antineoplastic Agents Drug Carriers Polymethacrylic Acids polycarboxybetaine methacrylate Betaine 3SCV180C9W Polyethylene Glycols 3WJQ0SDW1A mehr... Doxorubicin 80168379AG
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520 |a Polymer-drug conjugates are commonly used as nano drug vehicles (NDVs) to delivery anticancer drugs. Zwitterionic polymers are ideal candidates to conjugate drugs because they show higher resistance to nonspecific protein adsorption in complex media than that of nonionic water-soluble polymers, such as poly(ethylene glycol). However, the charge balance characteristics of zwitterionic polymers used as NDVs will be broken from the inclusion of additional charged groups brought by conjugated drugs or functional groups, leading to the loss of resistance to protein adsorption. Consequently, the nonspecific protein adsorption on drug carriers will cause fast clearance from the blood system, an immune response, or even severe systemic toxicity. To overcome this drawback, a model zwitterionic polymer, poly(carboxybetaine methacrylate) (pCBMA), was modified by the introduction of a negatively charged component, to neutralize the positive charge provided by the model drug, doxorubicin (DOX). A DOX-conjugated NDV which possesses excellent resistance to nonspecific protein adsorption was achieved by the formation of a strongly hydrated pCBMA shell with a slightly negative surface charge. This kind of DOX-conjugated NDV exhibited reduced cytotoxicity and prolonged circulation time, and it accelerated DOX release under mild acid conditions. In tumor-bearing mouse studies a 55% tumor-inhibition rate was achieved without causing any body weight loss. These results indicate the importance of charge tuning in zwitterionic polymer-based NDVs 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
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650 7 |a Drug Carriers  |2 NLM 
650 7 |a Polymethacrylic Acids  |2 NLM 
650 7 |a polycarboxybetaine methacrylate  |2 NLM 
650 7 |a Betaine  |2 NLM 
650 7 |a 3SCV180C9W  |2 NLM 
650 7 |a Polyethylene Glycols  |2 NLM 
650 7 |a 3WJQ0SDW1A  |2 NLM 
650 7 |a Doxorubicin  |2 NLM 
650 7 |a 80168379AG  |2 NLM 
700 1 |a Ma, Guanglong  |e verfasserin  |4 aut 
700 1 |a Zhang, Juan  |e verfasserin  |4 aut 
700 1 |a Lin, Weifeng  |e verfasserin  |4 aut 
700 1 |a Ji, Fangqin  |e verfasserin  |4 aut 
700 1 |a Bernards, Matthew T  |e verfasserin  |4 aut 
700 1 |a Chen, Shengfu  |e verfasserin  |4 aut 
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