A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain-Targeted Glioma Therapy.

Song, N; Lu, M; Liu, J; Lin, M; Shangguan, P; Wang, J; Shi, B; Zhao, J

A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain-Targeted Glioma Therapy.

Song, N Lu, M Liu, J Lin, M Shangguan, P Wang, J Shi, B

Zhao, J

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Publisher:: WILEY-V C H VERLAG GMBH
Publication Type:: Journal Article
Citation:: Angew Chem Int Ed Engl, 2024, 63, (10), pp. e202319700
Issue Date:: 2024-03-04

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Field	Value	Language
dc.contributor.author	Song, N
dc.contributor.author	Lu, M
dc.contributor.author	Liu, J
dc.contributor.author	Lin, M
dc.contributor.author	Shangguan, P
dc.contributor.author	Wang, J
dc.contributor.author	Shi, B https://orcid.org/0000-0002-1043-3163
dc.contributor.author	Zhao, J
dc.date.accessioned	2025-01-21T01:05:52Z
dc.date.available	2025-01-21T01:05:52Z
dc.date.issued	2024-03-04
dc.identifier.citation	Angew Chem Int Ed Engl, 2024, 63, (10), pp. e202319700
dc.identifier.issn	1433-7851
dc.identifier.issn	1521-3773
dc.identifier.uri	http://hdl.handle.net/10453/183899
dc.description.abstract	Giant heterometallic polyoxometalate (POM) clusters with precise atom structures, flexibly adjustable and abundant active sites are promising for constructing functional nanodrugs. However, current POM drugs are almost vacant in orthotopic brain tumor therapy due to the inability to effectively penetrate the blood-brain barrier (BBB) and low drug activity. Here, we designed the largest (3.0 nm × 6.0 nm) transition-metal-lanthanide co-encapsulated POM cluster {[Ce10 Ag6 (DMEA)(H2 O)27 W22 O70 ][B-α-TeW9 O33 ]9 }2 88- featuring 238 metal centers via synergistic coordination between two geometry-unrestricted Ce3+ and Ag+ linkers with tungsten-oxo cluster fragments. This POM was combined with brain-targeted peptide to prepare a brain-targeted nanodrug that could efficiently traverse BBB and target glioma cells. The Ag+ active centers in the nanodrug specifically activate reactive oxygen species to regulate the apoptosis pathway of glioma cells with a low half-maximal inhibitory concentration (5.66 μM). As the first brain-targeted POM drug, it efficiently prolongs the survival of orthotopic glioma-bearing mice.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY-V C H VERLAG GMBH
dc.relation.ispartof	Angew Chem Int Ed Engl
dc.relation.isbasedon	10.1002/anie.202319700
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	03 Chemical Sciences
dc.subject.classification	Organic Chemistry
dc.subject.classification	34 Chemical sciences
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Glioma
dc.subject.mesh	Brain Neoplasms
dc.subject.mesh	Drug Delivery Systems
dc.subject.mesh	Blood-Brain Barrier
dc.subject.mesh	Polyelectrolytes
dc.subject.mesh	Anions
dc.subject.mesh	Blood-Brain Barrier
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Glioma
dc.subject.mesh	Brain Neoplasms
dc.subject.mesh	Anions
dc.subject.mesh	Drug Delivery Systems
dc.subject.mesh	Polyelectrolytes
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Glioma
dc.subject.mesh	Brain Neoplasms
dc.subject.mesh	Drug Delivery Systems
dc.subject.mesh	Blood-Brain Barrier
dc.subject.mesh	Polyelectrolytes
dc.subject.mesh	Anions
dc.title	A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain-Targeted Glioma Therapy.
dc.type	Journal Article
utslib.citation.volume	63
utslib.location.activity	Germany
utslib.for	03 Chemical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
dc.date.updated	2025-01-21T01:05:49Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	63
utslib.citation.issue	10

Abstract:

Giant heterometallic polyoxometalate (POM) clusters with precise atom structures, flexibly adjustable and abundant active sites are promising for constructing functional nanodrugs. However, current POM drugs are almost vacant in orthotopic brain tumor therapy due to the inability to effectively penetrate the blood-brain barrier (BBB) and low drug activity. Here, we designed the largest (3.0 nm × 6.0 nm) transition-metal-lanthanide co-encapsulated POM cluster {[Ce10 Ag6 (DMEA)(H2 O)27 W22 O70 ][B-α-TeW9 O33 ]9 }2 88- featuring 238 metal centers via synergistic coordination between two geometry-unrestricted Ce3+ and Ag+ linkers with tungsten-oxo cluster fragments. This POM was combined with brain-targeted peptide to prepare a brain-targeted nanodrug that could efficiently traverse BBB and target glioma cells. The Ag+ active centers in the nanodrug specifically activate reactive oxygen species to regulate the apoptosis pathway of glioma cells with a low half-maximal inhibitory concentration (5.66 μM). As the first brain-targeted POM drug, it efficiently prolongs the survival of orthotopic glioma-bearing mice.

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http://hdl.handle.net/10453/183899