Issue 21, 2021

Development of curcumin-loaded zein nanoparticles for transport across the blood–brain barrier and inhibition of glioblastoma cell growth

Abstract

Glioblastoma (GBM) is a devastating primary brain tumor resistant to conventional therapies. A major obstacle to GBM treatment is the blood–brain barrier (BBB), or blood–glioma barrier, which prevents the transport of systemically administered (chemotherapeutic) drugs into the tumor. This study reports the design of dodecamer peptide (G23)-functionalized polydopamine (pD)-coated curcumin-loaded zein nanoparticles (CUR-ZpD-G23 NPs) that efficiently traversed the BBB, and delivered curcumin to glioblastoma cells. The NPs enhanced the cellular uptake of curcumin by C6 glioma cells compared to free curcumin, and showed high penetration into 3D tumor spheroids. Functionalization of the NPs with G23 stimulated BBB crossing and tumor spheroid penetration. Moreover, the NPs markedly inhibited proliferation and migration and induced cell death in liquid and soft agar models of C6 glioma cell growth. Fluorescence microscopy and flow cytometry studies showed that the CUR-ZpD-G23 NPs increased cellular ROS production and induced apoptosis of C6 glioma cells. Following in vivo intravenous injection in zebrafish, ZpD-G23 NPs demonstrated the ability to circulate, which is a first prerequisite for their use in targeted drug delivery. In conclusion, zein-polydopamine-G23 NPs show potential as a drug delivery platform for therapy of GBM, which requires further validation in in vivo glioblastoma models.

Graphical abstract: Development of curcumin-loaded zein nanoparticles for transport across the blood–brain barrier and inhibition of glioblastoma cell growth

Supplementary files

Article information

Article type
Paper
Submitted
10 sep 2020
Accepted
25 jan 2021
First published
28 jan 2021
This article is Open Access
Creative Commons BY license

Biomater. Sci., 2021,9, 7092-7103

Development of curcumin-loaded zein nanoparticles for transport across the blood–brain barrier and inhibition of glioblastoma cell growth

H. Zhang, W. L. van Os, X. Tian, G. Zu, L. Ribovski, R. Bron, J. Bussmann, A. Kros, Y. Liu and I. S. Zuhorn, Biomater. Sci., 2021, 9, 7092 DOI: 10.1039/D0BM01536A

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