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玛格妥昔单抗偶联聚乙二醇化聚酰胺-胺树形分子G4纳米复合物:一种用于抑制乳腺癌的智能纳米装置

Margetuximab conjugated-PEG-PAMAM G4 nano-complex: a smart nano-device for suppression of breast cancer.

作者信息

Khakinahad Yasaman, Sohrabi Saeedeh, Razi Shokufeh, Narmani Asghar, Khaleghi Sepideh, Asadiyun Mahboubeh, Jafari Hanieh, Mohammadnejad Javad

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Department of Biological and Biomedical Sciences, Cancer Biomedical Center, Tehran, Iran.

出版信息

Biomed Eng Lett. 2022 Apr 5;12(3):317-329. doi: 10.1007/s13534-022-00225-z. eCollection 2022 Aug.

Abstract

ABSTRACT

Breast cancer due to its high incidence and mortality is the second leading cause of death among females. On the other hand, nanoparticle-based drug delivery is one of the most promising approaches in cancer therapy, nowadays. Hence, margetuximab- and polyethylene glycol-conjugated PAMAM G4 dendrimers were efficiently synthesized for targeted delivery of quercetin (therapeutic agent) to MDA-MB-231 breast cancer cells. Synthesized nano-complexes were characterized using analytical devices such as FT-IR, TGA, DLS, Zeta potential analyzer, and TEM. The size less than 40 nm, - 18.8 mV surface charge, efficient drug loading capacity (21.48%), and controlled drug release (about 45% of drug release normal pH after 8 h) were determined for the nano-complex. In the biomedical test, the cell viability was obtained 14.67% at 24 h of post-treatment for 800 nM concentration, and IC was ascertained at 100 nM for the nano-complex. The expression of apoptotic Bax and Caspase9 genes was increased by more than eightfolds and more than fivefolds after treatment with an optimal concentration of nanocarrier. Also, more than threefolds of cell cycle arrest was observed at the optimal concentration synthetics, and 27.5% breast cancer cell apoptosis was detected after treatment with 100 nM nano-complex. These outputs have been indicating the potential capacity of synthesized nano-complex in inhibiting the growth of breast cancer cells.

摘要

摘要

乳腺癌因其高发病率和死亡率,成为女性死亡的第二大主要原因。另一方面,基于纳米颗粒的药物递送是当今癌症治疗中最具前景的方法之一。因此,高效合成了与玛格妥昔单抗和聚乙二醇共轭的PAMAM G4树枝状大分子,用于将槲皮素(治疗剂)靶向递送至MDA-MB-231乳腺癌细胞。使用傅里叶变换红外光谱仪、热重分析仪、动态光散射仪、zeta电位分析仪和透射电子显微镜等分析设备对合成的纳米复合物进行了表征。测定该纳米复合物的尺寸小于40nm,表面电荷为-18.8mV,药物负载效率高(21.48%),且药物释放可控(8小时后在正常pH下约45%的药物释放)。在生物医学测试中,对于800nM浓度的纳米复合物,处理后24小时细胞活力为14.67%,其半数抑制浓度确定为100nM。用最佳浓度的纳米载体处理后,凋亡相关的Bax和Caspase9基因的表达分别增加了八倍多和五倍多。此外,在最佳浓度的合成物处理下观察到细胞周期阻滞超过三倍,用100nM纳米复合物处理后检测到27.5%的乳腺癌细胞凋亡。这些结果表明合成的纳米复合物具有抑制乳腺癌细胞生长的潜在能力。

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