Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy
Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy
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DOI：
10.1016/j.biomaterials.2010.10.050
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发表时间：
2011-02-01
期刊：
影响因子：
14
通讯作者：
Ishizaka, Yukihito
中科院分区：
文献类型：
--
作者：
Kono, Kenji;Nakashima, Seiji;Ishizaka, Yukihito
为了开发肿瘤特异性化疗药物，我们设计了具有温度触发药物释放和磁共振成像（MRI）功能的脂质体。我们通过将具有约40 ° C的较低临界溶液温度的热敏性聚（2-乙氧基（乙氧基乙基）乙烯基醚）链和具有Gd 3+螯合残基的聚酰胺胺G3树枝状基脂质掺入聚乙二醇化脂质体中来制备多功能脂质体。这些稳定的多柔比星（DOX）负载脂质体在低于生理温度下将DOX保留在其内部，但在高于40摄氏度的温度下立即释放DOX。它们表现出优异的缩短纵向质子弛豫时间的能力。当静脉内给药至结肠26荷瘤小鼠时，肿瘤中蓄积的脂质体随时间增加，通过跟踪肿瘤中的T-1加权MRI信号强度，给药后8 h达到恒定水平。脂质体大小影响脂质体在肿瘤中的积累效率：直径约100 nm的脂质体比直径约50 nm的脂质体更有效地积累。肿瘤大小也影响蓄积：较大的肿瘤蓄积效率更高。当将负载有DOX的脂质体静脉内施用到荷瘤小鼠中并且在施用后8小时将肿瘤在44 ° C温和加热10分钟时，肿瘤生长被强烈抑制。具有温度触发药物释放和MRI功能的多功能脂质体可能产生个性化化疗，提供有效的患者优化化疗。(C)2010爱思唯尔有限公司版权所有。
For development of tumor-specific chemotherapy, we designed liposomes with temperature-triggered drug release and magnetic resonance imaging (MRI) functions. We prepared multi-functional liposomes by incorporating thermosensitive poly(2-ethoxy(ethoxyethyl)vinyl ether) chains with a lower critical solution temperatures around 40 degrees C and polyamidoamine G3 dendron-based lipids having Gd3+ chelate residues into pegylated liposomes. These stable doxorubicin (DOX)-loaded liposomes retained DOX in their interior below physiological temperature but released DOX immediately at temperatures greater than 40 degrees C. They exhibited excellent ability to shorten the longitudinal proton relaxation time. When administered intravenously into colon 26 tumor-bearing mice, accumulated liposomes in tumors increased with time, reaching a constant level 8 h after administration by following T-1-weighted MRI signal intensity in tumors. Liposome size affected the liposome accumulation efficiency in tumors: liposomes of about 100 nm diameter were accumulated more efficiently than those with about 50 nm diameter. Tumor size also affected accumulation: more efficient accumulation occurred in larger tumors. Tumor growth was strongly suppressed when liposomes loaded with DOX were administered intravenously into tumor-bearing mice and the tumor was heated mildly at 44 degrees C for 10 min at 8 h after administration. Multi-functional liposomes having temperature-triggered drug release and MRI functions might engender personalized chemotherapy, providing efficient patient-optimized chemotherapy. (C) 2010 Elsevier Ltd. All rights reserved.