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一种用于神经母细胞瘤治疗的改性碘苄胍共轭金纳米颗粒模型。

A model of modified -iodobenzylguanidine conjugated gold nanoparticles for neuroblastoma treatment.

作者信息

Saimuang Kween, Suttisintong Khomson, Kaewchangwat Narongpol, Thanayupong Eknarin, Wongngam Yodsathorn, Charoenphun Putthiporn, Wanotayan Rujira, Elaissari Abdelhamid, Hongeng Suradej, Polpanich Duangporn, Jangpatarapongsa Kulachart

机构信息

Center for Research and Innovation, Faculty of Medical Technology, Mahidol University Bangkok 10700 Thailand

National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA) Pathum Thani 12120 Thailand

出版信息

RSC Adv. 2021 Jul 20;11(41):25199-25206. doi: 10.1039/d1ra04054e. eCollection 2021 Jul 19.

Abstract

Iodine-131 -iodobenzylguanidine (I-IBG) has been utilized as a standard treatment to minimize adverse side effects by targeting therapies to bind to the norepinephrine transporter (NET) expressed on 90% of neuroblastoma cells. However, only a minority of patients who receive I-IBG radiotherapy have clinical responses, and these are usually not curative. In this study, novel ligand-conjugated gold nanoparticles (GNPs) based on IBG were synthesized and evaluated biologically with neuroblastoma cells . To induce specific internalization to the tumor cells and utilize it as a model for radioenhancement, I-modified IBG was successfully synthesized and grafted covalently to the surface of carboxylated PEG-GNPs. 49.28% of the novel IBG derivative was grafted on carboxylated PEG-GNPs. The particles were stable and not toxic to the normal fibroblast cell line, L929, even at the highest concentration tested (10 NPs per mL) at 24, 48, and 72 h. Moreover, the cellular uptake of the model was decreased significantly in the presence of a NET inhibitor, suggesting that there was specific internalization into neuroblastoma cells line (SH-SY5Y) the NET. Therefore, this model provides useful guidance toward the design of gold nanomaterials to enhance the efficiency of I-IBG treatment in neuroblastoma patients. However, the investigation of radio-therapeutic efficiency after radioisotope I substitution will be further conducted in a radiation safety laboratory using an animal model.

摘要

碘-131-碘苄胍(I-IBG)已被用作一种标准治疗方法,通过靶向疗法使其与90%的神经母细胞瘤细胞上表达的去甲肾上腺素转运体(NET)结合,以尽量减少不良副作用。然而,接受I-IBG放射治疗的患者中只有少数有临床反应,而且这些反应通常无法治愈。在本研究中,合成了基于IBG的新型配体共轭金纳米颗粒(GNP),并对其进行了神经母细胞瘤细胞的生物学评估。为了诱导肿瘤细胞特异性内化并将其用作放射增强模型,成功合成了I修饰的IBG,并将其共价接枝到羧基化PEG-GNP表面。49.28%的新型IBG衍生物接枝到羧基化PEG-GNP上。这些颗粒稳定,即使在24、48和72小时测试的最高浓度(每毫升10个纳米颗粒)下,对正常成纤维细胞系L929也无毒。此外,在存在NET抑制剂的情况下,模型的细胞摄取显著降低,这表明存在通过NET特异性内化到神经母细胞瘤细胞系(SH-SY5Y)中。因此,该模型为设计金纳米材料以提高I-IBG治疗神经母细胞瘤患者的效率提供了有用的指导。然而,放射性同位素I替代后的放射治疗效率研究将在辐射安全实验室中使用动物模型进一步进行。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1942/9037022/1c26d6650464/d1ra04054e-s1.jpg

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