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用于药物递送的环精氨酸-甘氨酸-天冬氨酸修饰红细胞:合成与评价

Cyclic arginine-glycine-aspartic acid-modified red blood cells for drug delivery: Synthesis and evaluation.

作者信息

Wang Chen, Wang Min, Zhang Yan, Jia Hongxin, Chen Binbin

机构信息

Department of Pharmaceutics, School of Pharmacy, Xiamen Medical College, Xiamen, Fujian, 361023, China.

Institute of Respiratory Diseases, Xiamen Medical College, Xiamen, Fujian, 361023, China.

出版信息

J Pharm Anal. 2022 Apr;12(2):324-331. doi: 10.1016/j.jpha.2021.06.003. Epub 2021 Jun 12.

Abstract

Red blood cells (RBCs) are an excellent choice for cell preparation research because of their biocompatibility, high drug loading, and long half-life. In this study, doxorubicin (DOX) was encapsulated with RBCs as the carrier. The biotin-avidin system binding principle was used to modify biotinylated cyclic arginine-glycine-aspartic acid (cRGD) onto RBC surfaces for accurate targeting, high drug loading, and sustained drug release. The RBC drug delivery system (DDS) was characterized, and the concentration of surface sulfur in the energy spectrum was 6.330%. The physical and chemical properties of RBC DDS were as follows: drug content, 0.857 mg/mL; particle size, 3339 nm; potential value, -12.5 mV; and cumulative release rate, 81.35%. There was no significant change in RBC morphology for up to seven days. The results of the targeting and cytotoxicity studies of RBC DDS showed that many RBCs covered the surfaces of U251 cells, and the fluorescence intensity was higher than that of MCF-7 cells. The IC value of unmodified drug-loaded RBCs was 2.5 times higher than that of targeted modified drug-loaded RBCs, indicating that the targeting of cancer cells produced satisfactory inhibition. This study confirms that the RBC DDS has the characteristics of accurate targeting, high drug loading, and slow drug release, which increases its likelihood of becoming a clinical cancer treatment in the future.

摘要

红细胞(RBCs)因其生物相容性、高载药量和长半衰期,是细胞制备研究的理想选择。在本研究中,阿霉素(DOX)被包裹于红细胞作为载体。利用生物素-抗生物素蛋白系统结合原理,将生物素化的环精氨酸-甘氨酸-天冬氨酸(cRGD)修饰到红细胞表面,以实现精准靶向、高载药量和药物缓释。对红细胞药物递送系统(DDS)进行了表征,能谱中表面硫的浓度为6.330%。红细胞DDS的物理化学性质如下:药物含量为0.857 mg/mL;粒径为3339 nm;电位值为-12.5 mV;累积释放率为81.35%。长达七天红细胞形态无显著变化。红细胞DDS的靶向性和细胞毒性研究结果表明,许多红细胞覆盖在U251细胞表面,荧光强度高于MCF-7细胞。未修饰的载药红细胞的IC值比靶向修饰的载药红细胞高2.5倍,表明对癌细胞的靶向作用产生了满意的抑制效果。本研究证实红细胞DDS具有精准靶向、高载药量和药物缓释的特点,这增加了其未来成为临床癌症治疗手段的可能性。

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