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氧化石墨烯纳米平台用于增强基于顺铂的药物递送在抗癌治疗中的应用。

Graphene Oxide Nanoplatforms to Enhance Cisplatin-Based Drug Delivery in Anticancer Therapy.

作者信息

Giusto Elena, Žárská Ludmila, Beirne Darren Fergal, Rossi Arianna, Bassi Giada, Ruffini Andrea, Montesi Monica, Montagner Diego, Ranc Vaclav, Panseri Silvia

机构信息

Institute of Science and Technology for Ceramics-National Research Council (CNR), 48018 Faenza (RA), Italy.

Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute, Palacký University Olomouc, 78371 Olomouc, Czech Republic.

出版信息

Nanomaterials (Basel). 2022 Jul 11;12(14):2372. doi: 10.3390/nano12142372.

Abstract

Chemotherapeutics such as platinum-based drugs are commonly used to treat several cancer types, but unfortunately, their use is limited by several side effects, such as high degradation of the drug before entering the cells, off-target organ toxicity and development of drug resistance. An interesting strategy to overcome such limitations is the development of nanocarriers that could enhance cellular accumulation in target cells in addition to decreasing associated drug toxicity in normal cells. Here, we aim to prepare and characterize a graphene-oxide-based 2D nanoplatform functionalised using highly branched, eight-arm polyethylene-glycol, which, owing to its high number of available functional groups, offers considerable loading capacity over its linear modalities and represents a highly potent nanodelivery platform as a versatile system in cancer therapy. The obtained results show that the GO@PEG carrier allows for the use of lower amounts of Pt drug compared to a Pt-free complex while achieving similar effects. The nanoplatform accomplishes very good cellular proliferation inhibition in osteosarcoma, which is strictly related to increased cellular uptake. This enhanced cellular internalization is also observed in glioblastoma, although it is less pronounced due to differences in metabolism compared to osteosarcoma. The proposed GO@PEG nanoplatform is also promising for the inhibition of migration, especially in highly invasive breast carcinoma (i.e., MDA-MB-231 cell line), neutralizing the metastatic process. The GO@PEG nanoplatform thus represents an interesting tool in cancer treatment that can be specifically tailored to target different cancers.

摘要

铂类药物等化疗药物常用于治疗多种癌症类型,但不幸的是,其应用受到多种副作用的限制,如药物在进入细胞前高度降解、脱靶器官毒性以及耐药性的产生。克服这些限制的一个有趣策略是开发纳米载体,除了降低正常细胞中相关药物的毒性外,还能增强靶细胞中的细胞摄取。在此,我们旨在制备并表征一种基于氧化石墨烯的二维纳米平台,该平台用高度分支的八臂聚乙二醇进行功能化修饰,由于其大量的可用官能团,与线性形式相比具有相当大的负载能力,并且作为癌症治疗中的通用系统代表了一种高效的纳米递送平台。所得结果表明,与无铂复合物相比,GO@PEG载体在达到相似效果的同时允许使用更低剂量的铂药物。该纳米平台在骨肉瘤中实现了非常好的细胞增殖抑制,这与细胞摄取增加密切相关。在胶质母细胞瘤中也观察到这种增强的细胞内化,尽管由于与骨肉瘤相比代谢存在差异,其不太明显。所提出的GO@PEG纳米平台在抑制迁移方面也很有前景,尤其是在高侵袭性乳腺癌(即MDA-MB-231细胞系)中,可中和转移过程。因此,GO@PEG纳米平台代表了癌症治疗中一种有趣的工具,可针对不同癌症进行专门定制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d86/9321599/a02772b4582c/nanomaterials-12-02372-g001.jpg

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