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

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.

Two Types of Subgroup-Valence Heteroatoms (PIII, TeIV) Synergistically Controlling Octa-CeIII-Encapsulated Heteropolyoxotungstate and Its Electrochemical Recognition Properties.

Rapid development of the synthetic chemistry of polyoxometalates (POMs) has greatly driven the generation of structurally variable innovative POM-based materials. Herein, we synthesized a novel PIII and TeIV synergistically controlling octa-CeIII-encapsulated heteropolyoxotungstate [H2N(CH3)2]11K2Na6H11[Ce8(CH3COO)2(HPIIIO3)2W8O20(H2O)12(B-ß-TeW8O30)2(B-α-TeW8O31)4]·64H2O (1). Its distinctive anion skeleton [Ce8(CH3COO)2(HPIIIO3)2W8O20(H2O)12(B-ß-TeW8O30)2(B-α-TeW8O31)4]30- is built by two tetra-vacancy [B-ß-TeW8O30]8- and four tetra-vacancy [B-α-TeW8O31]10- moieties linked through an inorganic-organic hybrid [Ce8(CH3COO)2(HPIIIO3)2W8O20(H2O)12]26+ {Ce8P2W8} cluster core. Interestingly, {Ce8P2W8} is assembled from four [W2O11]10- groups and two [HPIIIO3]2- anions and eight Ce3+ ions. Besides, 1 was further composited with carboxylated multiwalled carbon nanotube (CMCN), resulting in a bi-component 1/CMCN nanocomposite. An electrochemical recognition platform (named as 1/CMCN/GCE) was built by modifying 1/CMCN on a glassy carbon electrode (GCE) for electrochemical detection of dopamine (DPA) at physiological pH (pH = 7.0). The findings have shown that 1/CMCN/GCE exhibits a good detection limit of 4.95 nM for DPA. This work provides considerable inspiration to promote innovative and rational structure designs of POM-based materials and expand their applications to electrochemical and biological detection fields.