標的の薬物投与は,タンパク質のような分子構造を用いて行われる
Evonne M Rezler1, David R Khan, Janelle Lauer-Fields
1Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431, USA.
Journal of the American Chemical Society
|April 3, 2007
まとめ
ペプチドアンフィフィルを用いた標的型リポソームは,薬物投与において有望であることが示されています. これらのナノテクノロジーベースの薬物投与システム (ナノDDS) は,転移性メラノーマ細胞のCD44/コンドロイトン硫酸プロテオグリカン (CSPG) 受容体を選択的に標的にします.
科学分野:
- バイオテクノロジーとナノ医療
- マテリアルサイエンス 材料科学
- 細胞生物学 細胞生物学
背景:
- ナノテクノロジーベースの薬物投与システム (nanoDDS) は,標的治療のための強化された物理的,化学的,および生物学的特性を提供します.
- CD44/コンドロイトン硫酸プロテオグリカン (CSPG) 受容体は,転移性メラノーマでは過剰発現し,選択的な薬物投与の標的となる.
- タイプIVコラーゲン内のCD44/CSPGの結合配列が特定され,標的型リガンド設計が可能になりました.
研究 の 目的:
- CD44/CSPG受容体へのターゲティング配信のためのペプチド・アンフィフィール (PA) 機能化されたリポソームの構築と評価.
- リポソームの脂質組成が安定性と標的の効率に及ぼす影響を調査する.
- 転移性メラノーマと線維芽細胞細胞系におけるPA-リポソームの細胞吸収と標的の特異性を評価する.
主な方法:
- CD44/CSPGを結合するように設計された三重螺旋ペプチド-アンフィフィール (alpha1(IV) 1263-1277 PA) の合成.
- alpha1(IV) 1263-1277 PAを様々な脂質組成 (DSPC,DPPC,DSPG,DLPC,コレステロール) のリポソームに組み込む.
- リポソームの安定性,細胞のフッ素ホルモンの供給,受容体媒介による吸収の評価は,競争抑制アッセイを介して行われます.
主要な成果:
- DSPC,DSPG,コレステロールで構成されたリポソームは,DPPCを含むものと比較して,より高い安定性を示した.
- alpha1(IV) 1263-1277PAはDPPCリポソームの安定性を高め,CD44/CSPG発現する細胞に選択的なフッ素ホルモンの供給を示した.
- ターゲティング特異性は,外因性アルファ1 (IV) 1263-1277.7との前インキュベーション時にフッ素ホルモンの投与量の量に依存する減少によって確認されました.
結論:
- ペプチドアンフィフィール標的型リポソームは,薬物投与アプリケーションのために合理的に設計され,微調整することができます.
- リポソームの脂質組成は,システムの安定性と性能に大きな影響を与えます.
- alpha1(IV) 1263-1277 PAリポソームは,CD44/CSPG陽性転移性メラノーマの標的となるナノDDSとして潜在性を示しています.
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