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载铂氧化石墨烯:用于高效基因-化疗联合癌症治疗的纳米平台。

Platinated graphene oxide: A nanoplatform for efficient gene-chemo combination cancer therapy.

机构信息

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China; Department of Pharmacy, the Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.

出版信息

Eur J Pharm Sci. 2018 Aug 30;121:319-329. doi: 10.1016/j.ejps.2018.06.009. Epub 2018 Jun 12.

Abstract

Cisplatin (CisPt) is one of the most effective antitumor drugs against a wide range of solid cancers, and recent studies have indicated that combination of CisPt and RNA interference (RNAi) agents would effectively enhance therapeutic index, while the development of simple yet robust dual-delivery systems still remains a challenge. Here, we demonstrated that platinated graphene oxide is an excellent platform to achieve such goal. Nano-Graphene oxide (NGO) was easily platinated by CisPt, and the resulting CisPt/NGO was characterized by several aspects. As a proof-of-concept, an antisense microRNA-21 (Anti-miR-21) was employed as a potential RNAi agent. While most previous work functionalized NGO with cationic polymers for gene delivery, we demonstrated that platinated NGO is a potent carrier to load Anti-miR-21 with improved capacity and adsorption stability. With Anti-miR-21 loading, the system displayed significantly enhanced cytotoxicity to cancer cells, suggesting a synergistic effect. Finally, the underlying mechanism of the improved efficacy was explored, which can be ascribed to the cell apoptosis induced by Anti-miR-21 for gene silencing. This work demonstrated platinated graphene oxide as an effective nanocarrier to co-deliver CisPt and gene therapy for the treatment of cancer.

摘要

顺铂(CisPt)是一种广泛用于多种实体瘤的最有效的抗肿瘤药物,最近的研究表明,顺铂与 RNA 干扰(RNAi)试剂联合使用将有效提高治疗指数,而开发简单而强大的双重递药系统仍然是一个挑战。在这里,我们证明了铂化氧化石墨烯是实现这一目标的理想平台。纳米氧化石墨烯(NGO)很容易被 CisPt 铂化,所得 CisPt/NGO 通过多个方面进行了表征。作为一个概念验证,采用反义 microRNA-21(Anti-miR-21)作为一种潜在的 RNAi 试剂。虽然之前的大多数工作都是通过阳离子聚合物对 NGO 进行功能化以用于基因传递,但我们证明了铂化 NGO 是一种有效的载体,可提高载药量和吸附稳定性来负载 Anti-miR-21。通过负载 Anti-miR-21,该系统对癌细胞显示出显著增强的细胞毒性,表明存在协同作用。最后,探索了提高疗效的潜在机制,可归因于 Anti-miR-21 诱导的基因沉默的细胞凋亡。这项工作证明了铂化氧化石墨烯作为一种有效的纳米载体,可用于顺铂和基因治疗的联合递药,用于癌症的治疗。

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