Engineering a pH-Sensitive Liposomal MRI Agent by Modification of a Bacterial Channel.
Engineering a pH-Sensitive Liposomal MRI Agent by Modification of a Bacterial Channel.
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DOI：
10.1002/smll.201704256
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Blount P
中科院分区：
文献类型：
--
作者：
Yang LM;Zheng H;Ratnakar JS;Adebesin BY;Do QN;Kovacs Z;Blount P
MscL 是一种细菌机械敏感通道，充当细胞紧急释放阀，保护细胞在外部渗透压下降时免于裂解。该通道具有极大的孔隙（30Å），可以纯化并重构为人造膜。此外，MscL 已被修改为响应其他外部刺激（包括 pH 值的变化）而打开。这些特性表明该通道具有作为触发“纳米孔”的潜力，可局部释放 MRI 造影剂和药物等囊泡内容物。为此，我们设计了多种 pH 触发 MscL 纳米阀。我们将它们重组为隐形囊泡，此前已证明它们可以逃避正常的体内清除并被动地积聚在发炎和恶性组织中。这些囊泡装载有 Gd-DOTA（一种 MRI 造影剂），并测试所得纳米器件释放 Gd-DOTA 的能力，这通过大量水质子自旋的纵向弛豫率 (R1) 的增强得到证明。我们已经确定了对生理 pH 变化敏感的纳米阀，但灵敏度和功效不同，因此提供了一系列可能在不同环境中有用的纳米阀。这些触发的纳米装置可用于递送诊断剂和治疗剂。
MscL is a bacterial mechanosensitive channel that serves as a cellular emergency release valve, protecting the cell from lysis upon a drop in external osmolarity. The channel has an extremely large pore (30Å) and can be purified and reconstituted into artificial membranes. Moreover, MscL has been modified to open in response to alternative external stimuli including changes in pH. These properties suggest this channel’s potential as a triggered “nanopore” for localized release of vesicular contents such as MRI contrast agents and drugs. Toward this end, we have engineered several variants of pH-triggered MscL nanovalves. We have reconstituted them into stealth vesicles previously been shown to evade normal in vivo clearance and passively accumulate in inflamed and malignant tissues. These vesicles were loaded with Gd-DOTA, an MRI contrast reagent, and the resulting nanodevices tested for their ability to release Gd-DOTA as evidenced by enhancement of the longitudinal relaxation rate (R1) of the bulk water proton spins. We have identified nanovalves that are responsive to physiological pH changes, but differ in sensitivity and efficacy, thus giving an array of nanovalves that could potentially be useful in different settings. These triggered nanodevices may be useful in delivering both diagnostic and therapeutic agents.
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影响因子：
3.7
作者：
Iscla, Irene;Wray, Robin;Blount, Paul
通讯作者：
Blount, Paul
DOI：
10.1007/978-1-60327-360-2_16
发表时间：
2010-01-01
期刊：
LIPOSOMES: METHODS AND PROTOCOLS, VOL 1
影响因子：
--
作者：
Kocer, Armagan
通讯作者：
Kocer, Armagan
影响因子：
4.6
作者：
DESREUX, JF
通讯作者：
DESREUX, JF
影响因子：
14.8
作者：
Kocer, Armagan;Walko, Martin;Feringa, Ben L.
通讯作者：
Feringa, Ben L.
影响因子：
12.6
作者：
Andersson, Martin;Okeyo, George;Duran, Randolph S.
通讯作者：
Duran, Randolph S.