Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Naka-ku, Sakai, Osaka, Japan.
Biomaterials. 2011 Feb;32(5):1387-95. doi: 10.1016/j.biomaterials.2010.10.050. Epub 2010 Nov 19.
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 °C and polyamidoamine G3 dendron-based lipids having Gd(3+) 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 °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 °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.
为了开发肿瘤特异性化疗，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 下低临界溶液温度的温敏聚[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 树状脂质体掺入聚乙二醇化脂质体中来制备多功能脂质体。这些稳定的阿霉素（DOX）负载脂质体在生理温度下将 DOX 保留在其内部，但在温度高于 40°C 时立即释放 DOX。它们表现出极好的缩短纵向质子弛豫时间的能力。当将其静脉内施用于结肠 26 荷瘤小鼠时，随时间推移，肿瘤中积累的脂质体增加，通过肿瘤中 T(1)-加权 MRI 信号强度跟踪，在给药 8 小时后达到恒定水平。脂质体大小影响脂质体在肿瘤中的积累效率：直径约为 100nm 的脂质体比直径约为 50nm 的脂质体更有效地积累。肿瘤大小也影响积累：在较大的肿瘤中发生更有效的积累。当将负载 DOX 的脂质体静脉内施用于荷瘤小鼠并在给药后 8 小时温和加热至 44°C 10 分钟时，肿瘤生长受到强烈抑制。具有温度触发药物释放和 MRI 功能的多功能脂质体可能引发个性化化疗，为患者提供高效的优化化疗。
