Research Center for Medicinal Chemistry, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Deajeon, 305-600, South Korea.
Nanoscale Res Lett. 2012 Aug 17;7(1):462. doi: 10.1186/1556-276X-7-462.
Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities (r1) of GdSL were 6.6 to 7.8 mM-1 s-1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.
为了提高药物的抗肿瘤疗效并降低相关的严重副作用，研究了用于肿瘤靶向的超声敏感（声敏）脂质体。具有 Gd(III) 的脂质体造影剂是一种纳米造影剂系统，可将造影剂高效且选择性地递送到病理部位。本研究的目的是制备 Gd(III)-DOTA 修饰的声敏脂质体（GdSL），它可以将模型药物阿霉素（DOX）递送到特定部位，同时能够进行磁共振（MR）成像。GdSL 是使用合成的 Gd(III)-DOTA-1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺脂质制备的。20-kHz 超声诱导的 GdSL 的声敏性导致 33%至 40%的 DOX 释放。GdSL 的弛豫率（r1）为 6.6 至 7.8 mM-1 s-1，高于 MR-bester®。根据超声的强度评估了 GdSL 的细胞内摄取特性。超声触发的 GdSL 的 DOX 细胞内摄取高于非超声触发的 GdSL。我们的研究结果表明，顺磁和声敏脂质体 GdSL 可能为分子成像和靶向药物递送提供一个多功能平台。
