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基于壳聚糖的纳米递药平台的构建及表征,以提高索拉非尼在肝癌中的抗癌效果。

Fabrication and characterization of nanodelivery platform based on chitosan to improve the anticancer outcome of sorafenib in hepatocellular carcinoma.

机构信息

Department of Medical Laboratory and Blood Bank, King Fahad Specialist Hospital-Tabuk, Tabuk, Saudi Arabia.

Nanomaterials Synthesis and Characterization Laboratory, Institute of Bioscience (IBS), Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

出版信息

Sci Rep. 2023 Jul 27;13(1):12180. doi: 10.1038/s41598-023-38054-4.

Abstract

Chitosan nanoparticles (CS NPs) showed promising results in drug, vaccine and gene delivery for the treatment of various diseases. The considerable attention towards CS was owning to its outstanding biological properties, however, the main challenge in the application of CS NPs was faced during their size-controlled synthesis. Herein, ionic gelation reaction between CS and sodium tripolyphosphate (TPP), a widely used and safe CS cross-linker for biomedical application, was exploited. The development of nanodelivery platform, namely Sorafenib-loaded chitosan nanoparticles (SF-CS NPs), was constructed in order to improve SF drug delivery to human Hepatocellular Carcinoma (HepG2) cell lines. The NPs were artificially fabricated using an ionic gelation technique. A number of CS NPs that had been loaded with an SF were prepared using different concentrations of sodium tripolyphosphate (TPP). These concentrations were 2.5, 5, 10, and 20 mg/mL, and they are abbreviated as SF-CS NPs 2.5, SF-CS NPs 5.0, SF-CS NPs 10, and SF-CS NPs 20 respectively. DLS, FTIR, XRD, HRTEM, TGA, and FESEM with EDX and TEM were used for the physiochemical characterisation of SF-CS NPs. Both DLS and HRTEM techniques demonstrated that smaller particles were produced when the TPP content was raised. In a PBS solution with a pH of 4.5, the SF exhibited efficient release from the nanoparticles, demonstrating that the delivery mechanism is effective for tumour cells. The cytotoxicity investigation showed that their anticancer effect against HepG2 cell lines was significantly superior than that of free SF. In addition, the nanodrug demonstrated an absence of any detectable toxicity to normal adult human dermal fibroblast (HDFa) cell lines. This is a step towards developing a more effective anticancer medication delivery system with sustained-release characteristics, which will ultimately improve the way cancer is managed.

摘要

壳聚糖纳米粒子(CS NPs)在治疗各种疾病的药物、疫苗和基因传递方面显示出了有希望的结果。CS 受到了相当大的关注,这要归功于其出色的生物特性,然而,CS NPs 在应用中面临的主要挑战是在其尺寸控制合成过程中。本文利用壳聚糖(CS)与三聚磷酸钠(TPP)之间的离子凝胶反应,TPP 是一种广泛用于生物医学应用的 CS 交联剂。为了提高索拉非尼(SF)向人肝癌(HepG2)细胞系的药物传递,构建了纳米递药平台,即负载索拉非尼的壳聚糖纳米粒子(SF-CS NPs)。这些 NPs 是通过离子凝胶技术人工制备的。使用不同浓度的三聚磷酸钠(TPP)制备了负载 SF 的 CS NPs。这些浓度分别为 2.5、5、10 和 20 mg/mL,分别缩写为 SF-CS NPs 2.5、SF-CS NPs 5.0、SF-CS NPs 10 和 SF-CS NPs 20。DLS、FTIR、XRD、HRTEM、TGA 和 FESEM 结合 EDX 和 TEM 用于 SF-CS NPs 的物理化学特性分析。DLS 和 HRTEM 技术都表明,当 TPP 含量增加时,会产生更小的颗粒。在 pH 值为 4.5 的 PBS 溶液中,SF 从纳米粒子中有效释放,表明传递机制对肿瘤细胞有效。细胞毒性研究表明,其对 HepG2 细胞系的抗癌作用明显优于游离 SF。此外,纳米药物对正常成人皮肤成纤维细胞(HDFa)细胞系没有任何可检测的毒性。这是朝着开发具有缓释特性的更有效的抗癌药物输送系统迈出的一步,最终将改善癌症的管理方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8e3/10374537/a70d8dca080f/41598_2023_38054_Fig1_HTML.jpg

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