Anti CD19-PAMAM G4-PEG nano-complex as a potential targeted delivery system against leukemia

IF 4 Q2 NANOSCIENCE & NANOTECHNOLOGY
Shirin Mahmoodi Khatoon Abadi, Pouria Ahmadisimab, Seyedeh Fatemeh Hosseini, Asghar Narmani, Sepideh Khaleghi, Hanieh Jafari, Javad Mohammadnejad
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Abstract

In recent decades, cancer has been dramatically leading to high amounts of death all over the world, and leukemia is one of the progressing cancers that should stop somehow. To prevent its health-threatening incidence, nanoparticle-based targeting drug delivery systems are crucially needed. As a result, the polyethylene glycol (P) modified and anti-CD19 antibody (Ab) decorated polyamidoamine (PAMAM G4: P) dendritic nano-complex was developed for effective delivery of sodium butyrate drug (D) to Reh6 leukemia cells in this research work. After the synthesis of the nano-complex, several analytical devices such as FT-IR, TGA, DLS, Zeta potential analyzer, and TEM were applied to the qualification and quantification of syntheses and conjugations. Nanometric size (less than 50 nm in diameter), −4.2 mV surface charge, high drug loading efficiency (14.42%), and appropriate controlled drug release (less than 50% within first 8 h at pH 7.4) profile at different pHs were observed for Ab-P-P-D nano-complex. In the biomedical phase, the MTT assay demonstrated 13.04% cell viability at 800 nM after 24 h of treatment. IC50 was obtained for 100 nM concentration. The Bcl2 and caspase9 genes were indicated less than half and more than 15 folds of expressions at post-treatment time, respectively. The cell cycle arrest was drastically depicted more than 15 folds of cell Reh6 suppression in comparison to control. Moreover, the leukemia cells treated with Ab-P-P-D have demonstrated 42.39% apoptosis which was potentially several folds more than control. These data have verified the potency of the nanocarrier as an effective drug delivery system.

抗CD19-PAMAM G4-PEG纳米复合物作为治疗白血病的潜在靶向递送系统
近几十年来,癌症在世界范围内导致了大量的死亡,白血病是一种进展中的癌症,应该以某种方式停止。为了预防其危害健康的发生,迫切需要基于纳米颗粒的靶向给药系统。因此,本研究开发了聚乙二醇(P)修饰和抗cd19抗体(Ab)修饰的聚氨基胺(PAMAM G4: P)树突状纳米复合物,用于将丁酸钠药物(D)有效递送至Reh6白血病细胞。在纳米配合物合成后,利用FT-IR、TGA、DLS、Zeta电位分析仪、TEM等分析仪器对合成物和共轭物进行定性和定量分析。在不同pH值下,Ab-P-P-D纳米配合物具有纳米尺寸(直径小于50 nm)、- 4.2 mV表面电荷、较高的载药效率(14.42%)和良好的控释(pH 7.4时前8 h控释量小于50%)。在生物医学阶段,MTT实验显示,在800 nM处理24 h后,细胞存活率为13.04%。浓度为100 nM时获得IC50。Bcl2和caspase9基因在处理后的表达量分别低于一半和超过15倍。与对照组相比,细胞周期阻滞被显著描述为细胞Reh6抑制的15倍以上。此外,用Ab-P-P-D处理的白血病细胞凋亡率为42.39%,可能是对照组的几倍。这些数据证实了纳米载体作为一种有效的药物递送系统的效力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Micro and Nano Systems Letters
Micro and Nano Systems Letters Engineering-Biomedical Engineering
CiteScore
10.60
自引率
5.60%
发文量
16
审稿时长
13 weeks
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