Hatami Elham, Mu Ying, Shields Deanna N, Chauhan Subhash C, Kumar Santosh, Cory Theodore J, Yallapu Murali M
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Biochem Biophys Rep. 2019 Jan 25;17:197-207. doi: 10.1016/j.bbrep.2019.01.007. eCollection 2019 Mar.
Our goal was to design nanocarriers that specifically target and deliver therapeutics to polarized macrophages. Mannose receptors are highly overexpressed on polarized macrophages. In this study, we constructed Pluronic® -F127 polymer and tannic acid (TA) based nanoparticles (F127-TA core nanoparticles) with varying mannose densities. The particle size of the optimized mannose-decorated F127-TA hybrid nanoparticles (MDNPs) was found to be ~ 265 nm with a negative zeta potential of ~ - 4.5 mV. No significant changes in the size and zeta potentials of nanoparticles were observed, which demonstrated structural integrity and stability of the nanoformulation. Physicochemical characteristics of MDNPs were evaluated by FTIR and TGA and demonstrated the presence of mannose units on surface nanoparticles. A mannose-dependent cellular targeting and uptake of MDNPs was found in U937 macrophages. The uptake process was found to vary directly with time and volume of MDNPs nanoparticles. The uptake pattern is higher in M2 than M1. This behavior was also evident from the instantaneous and superior binding profile of M2 macrophage lysate protein with MDNPs over that of M1 macrophage lysate protein. These results demonstrated that an appropriate mannose ligand density was confirmed, suggesting efficient targeting of M2. Altogether, these data support that the MDNPs formulation could serve as a targeted therapeutic guide in the generation of nanomedicine to treat various conditions as an anti-inflammation therapy.
我们的目标是设计能够特异性靶向极化巨噬细胞并向其递送治疗药物的纳米载体。甘露糖受体在极化巨噬细胞上高度过表达。在本研究中，我们构建了基于不同甘露糖密度的普朗尼克®-F127聚合物和单宁酸（TA）的纳米颗粒（F127-TA核心纳米颗粒）。经优化的甘露糖修饰的F127-TA杂化纳米颗粒（MDNP）的粒径约为265nm，ζ电位为负，约为 -4.5mV。未观察到纳米颗粒的尺寸和ζ电位有显著变化，这表明该纳米制剂的结构完整性和稳定性。通过傅里叶变换红外光谱（FTIR）和热重分析（TGA）对MDNP的物理化学特性进行了评估，结果表明表面纳米颗粒上存在甘露糖单元。在U937巨噬细胞中发现了MDNP的甘露糖依赖性细胞靶向和摄取。摄取过程发现与MDNP纳米颗粒的时间和体积直接相关。M2型巨噬细胞中的摄取模式高于M1型。从M2巨噬细胞裂解物蛋白与MDNP的瞬时和优异结合谱高于M1巨噬细胞裂解物蛋白这一点也可以明显看出这种行为。这些结果表明确定了合适的甘露糖配体密度，表明对M2型巨噬细胞有高效靶向性。总之，这些数据支持MDNP制剂可作为一种靶向治疗导向，用于生成纳米药物，作为抗炎疗法治疗各种病症。
