期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 197, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111384
关键词
Gold nanoparticles; Cyclic peptides; Drug delivery; Cell internalization; Cytotoxicity; Anticancer therapy
资金
- EU ERDF (FEDER)
- Spanish government [TEC2017-85059-C3-2-R]
Conjugation of cytostatic drugs to nanomaterials aims to improve their bioavailability and selectivity. Water-soluble gold nanoparticles were synthesized as transporters for synthetic cyclic peptides, showing stability and higher toxicity towards cancer cells with improved uptake.
Conjugation of cytostatic drugs to nanomaterials seeks to improve their low bioavailability and selectivity to overcome the important associated side effects. In this work, we aimed to synthesize water-soluble gold nanoparticles as transporters for synthetic cyclic peptides with a potential anticancer activity but with a limited bioavailability. The highly water-soluble nanoparticles (2.5 nm diameter gold core) are coated with a mixture of polyethylene glycol linkers, one bearing a terminal hydroxyl group for increasing dispersibility in water, and the second bearing a carboxylic acid group for peptide conjugation through amide bond formation. Peptide-functionalized particles have a 9.7 +/- 1.8 nm hydrodynamic diameter and are highly water-soluble and stable in solution for at least one year. The morphology of the gold cores as well as their organic coating was studied using Transmission Electron Microscopy, showing that the attachment of a limited number of peptides per nanoparticle leads to a uneven organic coating of two different thicknesses, one of 2.0 +/- 0.6 nm formed by polyethylene glycol linkers, and a second of 3.6 +/- 0.5 nm which includes the peptide. GNP significantly enhance the internalization of the cyclic peptide BPC734 in cells as compared to peptide in solution, with improved uptake in cancerous HT29 cells. Cytotoxicity studies show that peptide BPC734 in solution is toxic in the micromolar range, whereas peptide-functionalized particles are toxic at nanomolar peptide concentrations and with a significantly higher toxicity for cancerous cells. All these results, besides the stability and expected passive tumor targeting, make these particles a promising option for improving the bioavailability, efficacy, and selectivity in cancer therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据