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基于生物石墨烯的多功能纳米复合材料的设计在宫颈癌治疗中表现出细胞内药物递送。

Design of Bio-Graphene-Based Multifunctional Nanocomposites Exhibits Intracellular Drug Delivery in Cervical Cancer Treatment.

机构信息

Bio-materials and Nanomedicine Laboratory, Department of Human Genetics and Molecular Biology, School of Life Sciences, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.

Molecular Therapeutic Laboratory, Department of Biochemistry, Periyar University, Salem 636011, Tamil Nadu, India.

出版信息

ACS Appl Bio Mater. 2022 Jun 20;5(6):2956-2964. doi: 10.1021/acsabm.2c00280. Epub 2022 May 27.

Abstract

The advent of bio-nanotechnology has revolutionized nanodrug delivery by improving drug efficacy and safety. Nevertheless, acceptable carriers for therapeutic molecules are one of the most difficult challenges in drug delivery. Graphene material-based (GMB) and polymer-based drug-loaded nanocarriers have both demonstrated clinical advantages in delivering drugs of interest /. Cisplatin (CDDP) is an inorganic chemotherapeutic drug that is commonly used to treat a variety of cancers. However, its clinical use is associated with drug resistance and few side effects, which reduces its antitumor effects. Therefore, we developed a CDDP-loaded chitosan-functionalized graphene oxide nanocomposite (CDDP@CS-GO NC)-based nanodrug delivery system (NDDS). Flow cytometry and confocal imaging show that the CDDP@CS-GO NCs lead to significantly increased intracellular drug accumulation in tumor cells. Cancer cells take up the nanocomposite endocytosis and can generate intracellular reactive oxygen species (ROS) to increase mitochondrial membrane potential loss (Δψ) and enable cytochrome- release, followed by the dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. experiments demonstrated the excellent cancer therapeutic effect with few side effects of the carriers. CDDP@CS-GO NCs are expected to play an important role in responsive NDDSs for cancer therapy.

摘要

生物纳米技术的出现通过提高药物疗效和安全性彻底改变了纳米药物传递。然而,治疗分子的可接受载体是药物传递中最具挑战性的问题之一。基于石墨烯材料(GMB)和聚合物的载药纳米载体在递药方面均显示出临床优势。顺铂(CDDP)是一种常用的无机化疗药物,用于治疗多种癌症。然而,其临床应用与耐药性和较少的副作用相关,从而降低了其抗肿瘤作用。因此,我们开发了一种载顺铂壳聚糖功能化氧化石墨烯纳米复合材料(CDDP@CS-GO NC)的纳米药物递送系统(NDDS)。流式细胞术和共聚焦成像显示,CDDP@CS-GO NCs 导致肿瘤细胞内药物积累显著增加。癌细胞通过内吞作用摄取纳米复合材料,并能产生细胞内活性氧(ROS),导致线粒体膜电位丧失(Δψ)和细胞色素 c 释放,随后 Bcl-2 易位到细胞质中,激活 caspase-3 诱导癌细胞凋亡。体内实验证明了载体具有良好的癌症治疗效果和较少的副作用。CDDP@CS-GO NCs 有望在癌症治疗的响应性 NDDS 中发挥重要作用。

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