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

Q1 Environmental Science Toxicology Reports Pub Date : 2024-10-10 DOI:10.1016/j.toxrep.2024.101765

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

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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.

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基于 PAMAM 树枝状聚合物的甲氨蝶呤和小檗碱联合给药，用于靶向 Hela 癌细胞

聚酰胺胺树枝状聚合物（PAMAM）是一类用于靶向给药的合成高分子聚合物。PAMAM 树枝状聚合物的特点是结构纯净、纳米级尺寸可调、单分散性和多功能表面修饰。本研究的目的是研究甲氨蝶呤（MTX）与 PAMAM 树枝状聚合物的共价偶联，该树枝状聚合物负载有天然抗癌剂小檗碱（BER），用于靶向 HeLa 细胞。傅里叶变换红外光谱证实了负载有小檗碱的 MTX 共轭 PAMAM（MTX-PAMAM-BER）的成功制备，并利用动态光散射对粒度进行了评估。生物检测、MTT、流式细胞仪、ROS 水平评估和 DAPI 染色用于评估制备的纳米系统的细胞毒性效果。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，MTX-PAMAM-BER 处理的细胞中还出现了值得注意的 ROS 水平。最后，应该指出的是，所制备的 MTX-PAMAM-BER 协同给药纳米系统可能是一种很有前景的癌症治疗和靶向药物。

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