Boosting the anti-tumor performance of disulfiram against glioblastoma by using ultrasmall nanoparticles and HIF-1α inhibitor. (15th August 2022)

• Record Type: Journal Article
• Authors: Yang, Shuang; Han, Yaobao; Bao, Bolin; Hu, Chunhong; Li, Zhen
• Is Part Of: Composites. Number 243(2022)
• Publication Date: 2022-08-15
• Subjects: Glioblastoma -- Hypoxia -- Hypoxia-inducible factor-1 -- Ultrasmall nanoparticles -- Disulfiram; GBM glioblastoma -- HIF-1α hypoxia-inducible factor-1α -- BBB blood-brain barrier -- TME tumor microenvironment -- VEGF-A vascular endothelial growth factor-A -- DSF disulfiram -- EPR enhanced permeability and retention -- ROS reactive oxygen species -- DMSO dimethyl sulfoxide -- GLUT 1 glucose transporters 1 -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel -- PA photoacoustic -- HbO2 oxyhemoglobin -- TEM transmission electron microscopy -- DLS dynamic light scattering -- FTIR Fourier transform infrared spectroscopy -- XRD X-ray diffraction pattern -- XPS X-ray photoelectron spectroscopy -- TGA thermogravimetric analysis -- PBS phosphate buffer saline -- MEM minimum essential medium -- CLSM confocal laser scanning microscopy -- FBS fetal bovine serum -- MRI magnetic resonance imaging -- ICP-MS inductively coupled plasma–mass spectrometry; Composite materials -- Periodicals; Materials science -- Periodicals; Composite materials; Periodicals; Electronic journals; 620.118
• DOI: 10.1016/j.compositesb.2022.110117
• Languages: English
• ISSNs: 1359-8368

Abstract

Abstract: Glioblastoma (GBM) has a poor prognosis due to its aggressive growth and resistance to postoperative treatments. The hypoxic microenvironment plays a significant role in tumor growth, metastasis and its resistance to therapy, it is crucial to alleviate the hypoxia during treatment. Herein, we report that biomimetic ultrasmall Cu2- x Se nanoparticles modified with hypoxia-inducible factor-1α (HIF-1α) inhibitor and coated with tumor cell membrane (abbreviated as CS-YC1@CM NPs) can effectively reduce the expression of HIF-1α to enhance the sensitivity of tumor cells to disulfiram and boost its therapeutic effect. We demonstrate that CS-YC1@CM NPs can effectively target tumor after temporarily opening the blood-brain barrier by focused ultrasound. The accumulated CS-YC1@CM NPs can serve a contrast agent of photoacoustic imaging for revealing the heterogeneity of hypoxia in tumor by the qualification of oxyhemoglobin from the photoacoustic images. More importantly, we show that the released copper ions from the CS-YC1@CM NPs can react with orally delivered disulfiram, which is usually used an alcohol-abuse drug, to in situ form the anti-tumor drug and effectively suppressed the growth of GBM. This work provides the insights for reutilizing the degradation products of nanoparticles and old drugs for new applications.