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载于温敏脂质体中的两性离子型硝普盐通过热激活可持续释放一氧化氮。

Heat-activated sustaining nitric oxide release from zwitterionic diazeniumdiolate loaded in thermo-sensitive liposomes.

机构信息

Center for Nanomedicine Research, National Health Research Institutes, Zhunan 350, Taiwan.

出版信息

Nitric Oxide. 2010 Aug 1;23(1):60-4. doi: 10.1016/j.niox.2010.04.003. Epub 2010 Apr 22.

DOI:10.1016/j.niox.2010.04.003
PMID:20399280
Abstract

Zwitterionic diazeniumdiolate, a nitric oxide precursor, was dissolved in basic buffer solution (pH=9.0) and encapsulated in thermo-sensitive liposomes composed of phospholipids of different sensitive temperatures. The basic intra-liposomal environment dramatically delayed spontaneous NO release. When the liposomes were placed in physiological buffer solution and temperatures were increased to the sensitive temperatures of the phospholipids' membranes, extra-liposomal protons started to influx to collapse the pH gradient and subsequently induce a significant NO release. Moreover, the presence of a stronger pH gradient when the liposomes were applied to a more acidic environment caused a higher proton influx driving force to trigger the influx of protons and, subsequently, NO release. In this work, we demonstrate that thermo-sensitive liposomes can be used to create a stable pH gradient in a nanoenvironment entrapping zwitterionic diazeniumdiolate for sustained and heat/acid-activated NO release.

摘要

两性离子二氮烯二酸盐,一种一氧化氮前体,溶解在碱性缓冲溶液(pH=9.0)中,并封装在由不同敏感温度的磷脂组成的温敏脂质体中。碱性的腔内环境极大地延迟了自发的一氧化氮释放。当脂质体被置于生理缓冲溶液中且温度升高到磷脂膜的敏感温度时,额外的脂质体质子开始内流以破坏 pH 梯度,从而随后诱导显著的一氧化氮释放。此外,当脂质体应用于更酸性的环境时,存在更强的 pH 梯度会导致更高的质子内流驱动力,以触发质子的内流,从而随后释放一氧化氮。在这项工作中,我们证明了温敏脂质体可用于在纳米环境中产生稳定的 pH 梯度,从而将两性离子二氮烯二酸盐包封起来,以实现持续的、热/酸激活的一氧化氮释放。

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