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Thermosensitive nanoplatforms for photothermal release of cargo from liposomes under intracellular temperature monitoring

机译:在细胞内温度监测下用于脂质体货物光热释放的热敏纳米平台

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Control of cargo release from nanoscale carriers is an important technology for maximizing the benefits of nanoparticulate drug delivery systems. Herein, we attempt to trigger the release of cargo from liposomes by photothermal conversion of water with a 980 nm near-infrared (NIR) laser. This study examined liposomes of two types formulated by 1,2-dipalmitory-sn-glycero-3-phosphocholine (DPPC) or a mixture of DPPC/cholesterol with an anionic lipid and PEG-lipid as stabilizers encapsulating calcein as a cargo at different ionic strengths. Liposome formulation encapsulating a hypertonic solution with a lipid membrane shows that a gel to liquid-crystalline phase transition at around 40 degrees C effectively released the cargo from liposomes at temperature above 40 degrees C with NIR irradiation. Our proof of concept has been further demonstrated in a cancer cell with monitoring the actual "intracellular temperature" using a fluorescent thermosensor. Intracellular thermometry revealed that it was not until the intracellular temperature reached around 40 degrees C by NIR irradiation that the release of the cargo started gradually, showing good agreement with the result from the extracellular in vitro study. This targeted release of cargo from thermosensitive liposomes based on a photothermal effect using a NIR laser offers a potent nanoscale platform for the on-demand release of drugs in intracellular space with local hyperthermia. The intracellular thermometry facilitates the quantitative monitoring and control of the hyperthermia at the cellular level.
机译:从纳米级载体释放货物的控制是使纳米颗粒药物递送系统的利益最大化的一项重要技术。本文中,我们尝试通过使用980 nm近红外(NIR)激光对水进行光热转化来触发从脂质体释放货物。这项研究检查了两种类型的脂质体,它们由1,2-二棕榈酸酯-sn-甘油-3-磷酸胆碱(DPPC)或DPPC /胆固醇与阴离子脂质和PEG-脂质的混合物配制作为稳定剂,将钙黄绿素作为货物包裹在不同离子下长处用脂质膜包裹高渗溶液的脂质体制剂显示,在40摄氏度左右的温度下,通过NIR辐照,凝胶到液晶的相变有效地从脂质体释放了货物。通过使用荧光热传感器监测实际的“细胞内温度”,我们的概念证明已在癌细胞中得到进一步证明。细胞内测温显示直到通过NIR辐射细胞内温度达到约40℃,才开始逐渐释放货物,这与细胞外体外研究的结果显示出良好的一致性。基于使用NIR激光的光热效应,有针对性地从热敏脂质体中释放货物,提供了一个强大的纳米级平台,可以通过局部热疗按需释放细胞内空间中的药物。细胞内测温有助于在细胞水平上定量监测和控制体温过高。

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