脂质包覆的 pH 敏感的磷酸镁颗粒用于细胞内蛋白质递送。
Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery.
机构信息
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, California, 95211, USA.
出版信息
Pharm Res. 2019 Apr 11;36(6):81. doi: 10.1007/s11095-019-2607-6.
PURPOSE
To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery.
METHODS
Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering. The pH-sensitivity of LPP-CAT was determined by monitoring their degradation of hydrogen peroxide (HO) and their morphologies under transmission electron microscopy (TEM) at pH 7.4 and 5.5. The ability of LPP-CAT to protect MCF-7 cells against hydrogen peroxide was measured by MTS assay. ROS levels in EA.hy926 cells were measured after treatment with LPP-CAT.
RESULTS
LPP-CAT were successfully prepared and carried an average diameter of <300 nm and ζ -potential of about +40 mV. At pH 5.5, LPP-CAT degraded HO almost 4-fold as fast as pH 7.4 and displayed drastic morphological changes of an osmotic explosion. LPP-CAT protected MCF-7 cells from lethal level of exogenous HO and significantly lowered the ROS levels in EA.hy926 cells. A lipid with a pH-sensitive conformational switch (flipid) further enhanced the protein delivery of LPP-CAT.
CONCLUSION
LPP represents a promising nano-system for intracellular protein delivery.
目的
开发带正电荷的脂质包裹的磷酸镁纳米颗粒（LPP），用于细胞内过氧化氢酶（CAT）的递送。
方法
通过微乳液沉淀法制备磷酸镁纳米颗粒（MgP NP），并将其与负载 CAT 的阳离子脂质体（DOTAP/胆固醇）混合，得到 CAT 的 LPP 制剂（LPP-CAT）。通过动态光散射测量 LPP-CAT 的粒径和 ζ 电位。通过监测其在 pH 7.4 和 5.5 下对过氧化氢（HO）的降解以及透射电子显微镜（TEM）下的形态变化来测定 LPP-CAT 的 pH 敏感性。通过 MTS 测定法测量 LPP-CAT 保护 MCF-7 细胞免受过氧化氢的能力。处理 EA.hy926 细胞后，测量细胞内活性氧（ROS）水平。
结果
成功制备了 LPP-CAT，其平均粒径<300nm，ζ 电位约为+40mV。在 pH 5.5 下，LPP-CAT 降解 HO 的速度比 pH 7.4 时快近 4 倍，并且表现出渗透爆炸的剧烈形态变化。LPP-CAT 可保护 MCF-7 细胞免受外源性 HO 的致命影响，并显著降低 EA.hy926 细胞中的 ROS 水平。具有 pH 敏感构象开关（flipid）的脂质进一步增强了 LPP-CAT 的蛋白递送。
结论
LPP 是一种有前途的细胞内蛋白递送纳米系统。
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