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叶酸修饰的壳聚糖纳米颗粒用于双核钴(II)配合物在癌症治疗中的靶向递送。

Folic acid-modified chitosan nanoparticles for targeted delivery of a binuclear Co(II) complex in cancer therapy.

作者信息

Ragheb Mohamed A, Ragab Mona S, Mahdy Fatma Y, Elsebaie Mohamed S, Saber Amal M, AbdElmalak Youstina O, Elsafoury Reem H, Elatreby Amal A, Rochdi Ahmed M, El-Basyouni Ahmed W, Shoukry Mohamed M, Eldeeb Mohamed A, El-Sherif Rabab M, Abdelhamid Ismail A, Salah-Eldin Doaa S

机构信息

Chemistry Department (Biochemistry Division), Faculty of Science, Cairo University, Giza, P.O. 12613, Egypt; Biotechnology Department, Faculty of Nanotechnology for Postgraduate Studies, Cairo University, Sheikh Zayed Branch Campus, Giza 12588, Egypt.

Chemistry Department, Faculty of Science, Cairo University, Giza, P.O. 12613, Egypt.

出版信息

Int J Biol Macromol. 2025 Jun;311(Pt 4):144034. doi: 10.1016/j.ijbiomac.2025.144034. Epub 2025 May 7.

Abstract

A salient challenge in cancer chemotherapy is the successful delivery of drugs to cancer cells. Therapeutic agents can be delivered to cancer cells in a targeted and efficient manner using nanoparticles (NPs). Herein, we present the molecular characterization of a novel binuclear Co(II) complex with octahedral geometry based on Schiff base from dehydroacetic acid and piperazine derivatives. DNA and BSA binding interactions were investigated using UV-Vis spectroscopy and gel electrophoresis. In vitro cytotoxicity of Co(II) complex was assessed against microbes and human cells (Cancer: MDA-MB-231, MCF7, A375, HepG2; Non-cancerous: HSF, WI-38) using well diffusion and MTT assays. Chitosan decorated with folic acid (CS-FA) was fabricated to encapsulate Co(II) complex, which may serve as a nano-targeted drug delivery system, to dampen its adverse effects on non-cancerous cells. TEM and DLS analysis confirmed nano-sized and stable monodisperse nanosuspension of both (CS-FA) and (CS-FA-Co(II) complex) systems. CS-FA-Co(II) complex NPs exhibited an 8.3-fold increase in cytotoxicity against folate-receptor-positive MDA-MB-231 cells, while remaining safe for folate-receptor-negative HSF cells. They also induced cell cycle arrest, inhibited migration, and triggered apoptosis by modulating Bax, Bcl-2, caspase-3, and CDH1. These findings highlight CS-FA NPs as a promising targeted delivery system for Co(II) complex-based cancer therapeutic agents, offering improved efficacy.

摘要

癌症化疗中的一个突出挑战是如何成功地将药物递送至癌细胞。使用纳米颗粒(NPs)可以以靶向且高效的方式将治疗剂递送至癌细胞。在此,我们展示了一种基于脱氢乙酸和哌嗪衍生物的席夫碱的具有八面体几何结构的新型双核Co(II)配合物的分子表征。使用紫外可见光谱和凝胶电泳研究了DNA和牛血清白蛋白的结合相互作用。使用平板扩散法和MTT法评估了Co(II)配合物对微生物和人类细胞(癌症细胞:MDA-MB-231、MCF7、A375、HepG2;非癌细胞:HSF、WI-38)的体外细胞毒性。制备了用叶酸修饰的壳聚糖(CS-FA)来包裹Co(II)配合物,其可作为一种纳米靶向药物递送系统,以减轻其对非癌细胞的不良影响。透射电子显微镜(TEM)和动态光散射(DLS)分析证实了(CS-FA)和(CS-FA-Co(II)配合物)系统均为纳米尺寸且稳定的单分散纳米悬浮液。CS-FA-Co(II)配合物纳米颗粒对叶酸受体阳性的MDA-MB-231细胞的细胞毒性增加了8.3倍,而对叶酸受体阴性的HSF细胞仍保持安全。它们还通过调节Bax、Bcl-2、caspase-3和CDH1诱导细胞周期停滞、抑制迁移并引发细胞凋亡。这些发现突出了CS-FA纳米颗粒作为基于Co(II)配合物的癌症治疗剂的一种有前景的靶向递送系统,具有更高的疗效。

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