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

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 repo...

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Bibliographic Details
Published in:Biomaterials science 2021-10, Vol.9 (21), p.792-713
Main Authors: Zhang, Huaiying, van Os, Winant L, Tian, Xiaobo, Zu, Guangyue, Ribovski, Laís, Bron, Reinier, Bussmann, Jeroen, Kros, Alexander, Liu, Yong, Zuhorn, Inge S
Format: Article
Language:English
Subjects:
Apoptosis
Blood-brain barrier
Brain cancer
Cell death
Cell growth
Cellular manufacture
Flow cytometry
Fluorescence
Nanoparticles
Penetration
Spheroids
Tumors
Zebrafish
Zein
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Summary: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. Zein-polydopamine nanoparticles functionalized with G23 peptide cross an in vitro blood-brain barrier and penetrate tumor spheroids. When loaded with curcumin they effectively reduce proliferation, migration, and viability of C6 glioma cells.
ISSN:2047-4830
2047-4849
DOI:10.1039/d0bm01536a