Eldin Samar S Ezz, Rashed Hassan M, Hassan Amira H, Salem Heba F, Sakr Tamer M
Department of Radiation Protection, Nuclear and Radiation Safety Research Center, Egyptian Atomic Energy Authority, Cairo 13759, Egypt.
Department of Labeled Compounds, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo 13759, Egypt.
Curr Drug Deliv. 2023;20(4):387-399. doi: 10.2174/1567201819666220325092122.
5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages.
This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects.
5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of Tc-5-aza solution and Tc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor).
5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. Tc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the Tc-5-azacitidine solution.
Tc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, Tc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer.
5-氮杂胞苷是一种非常有效的化疗药物，但存在某些缺点。
本研究旨在制备金纳米颗粒作为5-氮杂胞苷的一种新的纳米制剂，以提高其生物利用度并降低其副作用。
制备了负载5-氮杂胞苷的GA-AuNPs，并通过紫外-可见光谱、红外光谱（IR）和电子透射显微镜（TEM）进行表征。通过测量其zeta电位、粒径和载药效率对这个新平台进行体外表征，并评估其对MCF-7细胞系的抗增殖作用。通过不同给药途径（静脉内和瘤内）在荷瘤小鼠中进行了Tc-5-氮杂胞苷溶液和Tc-5-氮杂胞苷-金纳米制剂的体内生物分布研究。
成功制备了5-氮杂胞苷-GA-AuNPs制剂，最佳粒径约为34.66 nm，zeta电位为-14.4 mV，包封率高。成功地放射性合成了Tc-5-氮杂胞苷-GA-AuNPs，标记产率为95.4%。生物分布研究表明，与Tc-5-氮杂胞苷溶液相比，5-氮杂胞苷-GA-AuNPs制剂在肿瘤中的选择性积累高，在非靶器官中的摄取低。
Tc-5-氮杂胞苷-GA-AuNPs提高了5-氮杂胞苷在癌症中的选择性和摄取。此外，Tc-5-氮杂胞苷-GA-AuNPs可作为有前景的癌症治疗诊断放射性药物制剂。
