Effect of Cholesterol on Nano-Structural Alteration of Light-Activatable Liposomes via Laser Irradiation: Small Angle Neutron Scattering Study.
Effect of Cholesterol on Nano-Structural Alteration of Light-Activatable Liposomes via Laser Irradiation: Small Angle Neutron Scattering Study.
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DOI：
10.1016/j.colsurfa.2022.128548
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发表时间：
2022-02
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影响因子：
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通讯作者：
Zheng Yuan;Saikat Das;Changwoo Do;Yoonjee C. Park
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作者：
Zheng Yuan;Saikat Das;Changwoo Do;Yoonjee C. Park
尽管光激活脂质体已经被广泛研究用于药物递送应用，但是基于脂质组合物的药物释放的基本机制尚未完全理解。特别是，尽管胆固醇在脂质组合物中的广泛使用，胆固醇在光活化药物释放中的作用尚未研究。本文研究了胆固醇对光响应性药物脂质体经近红外激光激活后释放的影响。我们制备了甲氨蝶呤（MTX）包封的DSPC脂质体，其由0 mol%（单键Chol）或35 mol%胆固醇（+Chol）组成，在脂质双层上具有（+Au）或不具有金纳米棒（单键Au），以比较激光照射后的药物释放、形态学变化和纳米结构。透射电子显微镜（TEM）和小角中子散射（SANS）数据显示，只有+Chol +Au脂质体显示激光照射后的脂质体的部分聚集。当脂质体被加热到链转变温度以上时，观察到类似的药物释放和结构变化趋势。总体而言，我们已经发现：（1）包含35摩尔%胆固醇增强了高于Tc的脂质双层的渗透性;（2）激光激活的脂质体药物递送的机制是在等离子体材料存在下通过光热效应破坏脂质双层膜。通过了解该技术的基本原理，可以预期在靶向部位精确控制药物释放，并具有良好的稳定性和可重复性。
Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (single bondChol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (single bondAu) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.