Boosting the anti-tumor performance of disulfiram against glioblastoma by using ultrasmall nanoparticles and HIF-1α inhibitor

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-xSe 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.