Sahoo Kaustuv, Koralege Rangika S Hikkaduwa, Flynn Nicholas, Koteeswaran Samyukta, Clark Peter, Hartson Steve, Liu Jing, Ramsey Joshua D, Pope Carey, Ranjan Ashish
Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
Pharm Res. 2016 May;33(5):1191-203. doi: 10.1007/s11095-016-1864-x. Epub 2016 Jan 26.
Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function.
The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP).
Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC.
ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules.
纳米颗粒（NP）附着于生物相容性二级载体（如红细胞（RBC））可延长药物分子在血液中的停留时间，并有助于开发下一代纳米治疗药物。然而，关于红细胞靶向纳米颗粒对红细胞功能的影响知之甚少。
本研究的目的是在体外开发并表征一种新型的基于聚-L-赖氨酸（PLL）和聚乙二醇（PEG）共聚物的纳米颗粒，其包含荧光标记的牛血清白蛋白（BSA），并与ERY1偶联，ERY1是一种对红细胞膜蛋白血型糖蛋白A具有高亲和力的12氨基酸肽（ENP）。
共聚焦和流式细胞术数据表明，ENP能有效且不可逆地与红细胞结合，在生理流动循环模型中，24小时后约70%的红细胞被结合，而没有ERY1的纳米颗粒的结合率为10%。在这些条件下，合成的ENP对红细胞无毒。在所施加的剪切力（0 - 15 Pa）下的流变学参数不受ENP附着于红细胞的影响。然而，在高浓度下，ENP对血型糖蛋白A的强亲和力降低了红细胞的变形能力。
ENP可以有效地附着于红细胞，而不会对细胞功能产生不利影响，这可能会提高药物分子的循环半衰期。
