Doxorubicin‐Loaded Polymeric Micelle Overcomes Multidrug Resistance of Cancer by Double‐Targeting Folate Receptor and Early Endosomal pH
書誌事項
- 公開日
- 2008-11
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1002/smll.200701275
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>An optimized, pH‐sensitive mixed‐micelle system conjugated with folic acid is prepared in order to challenge multidrug resistance (MDR) in cancers. The micelles are composed of poly(histidine (His)‐<jats:italic>co</jats:italic>‐phenylalanine (Phe))‐<jats:italic>b</jats:italic>‐poly(ethylene glycol) (PEG) and poly(L‐lactic acid) (PLLA)‐<jats:italic>b</jats:italic>‐PEG‐folate. Core‐forming, pH‐sensitive hydrophobic blocks of poly(His‐<jats:italic>co</jats:italic>‐Phe) of varying composition are synthesized. The pH sensitivity of the micelles is controlled by the copolymer composition and is fine tuned to early endosomal pH by blending PLLA(3K)‐<jats:italic>b</jats:italic>‐PEG(2K)‐folate in the presence of a basic anticancer drug, doxorubicin (DOX). In vitro tests are conducted against both wild‐type (A2780) and DOX‐resistant ovarian carcinoma cell lines. A mixed‐micelle system composed of poly(His‐co‐Phe (16 mole%))‐<jats:italic>b</jats:italic>‐PEG (80 wt%) and PLLA‐<jats:italic>b</jats:italic>‐PEG‐folate (20 wt%) is selected to target early endosomal pH. DOX‐loaded micelles effectively kill both wild‐type sensitive (A2780) and DOX‐resistant ovarian MDR cancer‐cell lines (A2780/DOX<jats:sup>R</jats:sup>) through an instantaneous high dose of DOX in the cytosol, which results from active internalization, accelerated DOX release triggered by endosomal pH, and an endosomal membrance disruption.</jats:p>
収録刊行物
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- Small
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Small 4 (11), 2043-2050, 2008-11
Wiley