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基于聚酰胺-胺(PAMAM)树枝状大分子的甲氨蝶呤和黄连素共递送用于靶向HeLa癌细胞

PAMAM dendrimers based co-delivery of methotrexate and berberine for targeting of Hela cancer cells.

作者信息

Majidzadeh Hossein, Araj-Khodaei Mostafa, Aghanejad Ayuob, Ghaffari Maryam, Jafari Amir, Jenanifard Forough, Ezzati Nazhad Dolatabadi Jafar, Andishmand Hashem, Hamblin Michael R

机构信息

Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Persian Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Toxicol Rep. 2024 Oct 10;13:101765. doi: 10.1016/j.toxrep.2024.101765. eCollection 2024 Dec.

Abstract

Polyamidoamine dendrimer (PAMAM) is a class of synthetic macromolecular polymers for targeted drug delivery. PAMAM dendrimers are characterized by a pure defined structure, adjustable nanoscale dimensions, mono-dispersity, and versatile surface modification. The objective of this study was to study the covalent coupling of methotrexate (MTX) to PAMAM dendrimer, which was loaded with the natural product anticancer agent, berberine (BER) for the targeting of HeLa cells. The successful preparation of MTX-conjugated PAMAM loaded with BER (MTX-PAMAM-BER) was confirmed by Fourier transform infrared spectroscopy and particle size was evaluated using dynamic light scattering. The biological assays, MTT, flow cytometry, ROS levels evaluation and DAPI staining were used to assess the cytotoxicity effect of the prepared nanosystem. The findings indicated that MTX-PAMAM-BER exhibited greater suppression of tumor cell growth in comparison to BER, MTX, PAMAM-BER, and MTX-PAMAM. Besides, the noteworthy ROS level has been seen in the treated cells with MTX-PAMAM-BER. Finally, it should be stated that the fabricated MTX-PAMAM-BER co-delivery nanosystem could be a promising agent for cancer therapy and targeting.

摘要

聚酰胺-胺型树枝状大分子(PAMAM)是一类用于靶向给药的合成高分子聚合物。PAMAM树枝状大分子的特点是结构明确、纳米尺寸可调、单分散性以及表面修饰多样。本研究的目的是研究甲氨蝶呤(MTX)与PAMAM树枝状大分子的共价偶联,该树枝状大分子负载了天然产物抗癌剂黄连素(BER)用于靶向HeLa细胞。通过傅里叶变换红外光谱证实了负载BER的MTX偶联PAMAM(MTX-PAMAM-BER)的成功制备,并使用动态光散射评估了粒径。采用MTT、流式细胞术、ROS水平评估和DAPI染色等生物学试验来评估所制备纳米系统的细胞毒性作用。研究结果表明,与BER、MTX、PAMAM-BER和MTX-PAMAM相比,MTX-PAMAM-BER对肿瘤细胞生长的抑制作用更强。此外,在用MTX-PAMAM-BER处理的细胞中观察到了显著的ROS水平。最后,应该指出的是,所制备的MTX-PAMAM-BER共递送纳米系统可能是一种有前途的癌症治疗和靶向药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe08/11525225/e9abdde86bc6/ga1.jpg

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