A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain‐Targeted Glioma Therapy

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 {[Ce10Ag6(DMEA)(H2O)27W22O70][B‐α‐TeW9O33]9}288– 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 glioma cell apoptosis pathway 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.

{SeO2(OH)} Bridging Lanthanide-Containing Antimono-Seleno-Tungstates

“…As an important subfamily, Ln-containing POMs have experienced rapid development and achieved great advancement over the past few decades. In terms of Ln ions, they possess strong affinity for oxygen, flexible coordination, and bonding modes, which make them more versatile in their connection with nucleophilic POM fragments and facilitate the construction of functional cluster materials with novel structures. − To date, a large number of Ln-containing POMs have been reported, with some representative structures including [Gd 8 As 12 W 124 O 432 (H 2 O) 22 ] 60– , [{(XO 3 )W 10 O 34 } 8 {Ce 8 (H 2 O) 20 }​(WO 2 ) 4 (W 4 O 12 )] 48– (X = Se, Te), [(Ln 14 (H 2 O)​W 4 (OH)​O 14 )​(WO 4 ) 4 (GeW 10 O 38 ) 6 ] 43– (Ln = Eu, Gd, Tb, Dy, Ho, Er), [Ce 16 As 12 (H 2 O) 36 W 148 O 524 ] 76– , [Ce 20 Ge 10 W 100 O 376 (OH) 4 (H 2 O) 30 ] 56– , [K 8 Ce 24 Ge 12 W 120 O 456 (OH) 12 (H 2 O) 64 ] 52– , [Ln 27 Ge 10 W 106 O 406 (OH) 4 (H 2 O) 24 ] 59– (Ln = La, Ce), [Ln 30 Ge 12 W 107 O 420 (OH) 2 (H 2 O) 14 ] 62– (Ln = Sm, Eu), etc.…”

Polyoxometalates: metallodrug agents for combating amyloid aggregation

“…Crucially, their associated chemical properties, such as redox potential, acidity, polarity, and surface charge distribution, can be precisely tailored to specific needs by adjusting factors like composition, size, shape, and counterion [ 34 , 35 ]. These outstanding features gift POMs with multifarious bioactivities in the fight against cancer, viruses, diabetes, and bacteria [ 27 , 31 , 33 , 36–39 ]. The pharmacological and biological attributes of POMs are largely ascribed to their interactions with proteins [ 33 , 40 , 41 ].…”

Advances in polyoxometalate-based electrochemical sensors in the last three years

“…). 14–21 With the continuous development of synthetic methods, a large number of TM elements (such as Cu II , Fe III , Co II , etc. ), lanthanides (Ln) (such as La III , Ce III/IV , Pr III , Nd III , Sm III , Eu III , etc. )…”

“…and organic ligands (usually those containing coordination-active carboxyl, amidogen or hydroxy groups) have been introduced into the skeletons of POMs. 14–27 This situation undoubtedly contributes to an overwhelming diversity of molecular structures and unique properties, for example, photoluminescence/electroluminescence ability, reversible multi-electron transport capability, catalytic activity, and so on. Therefore, POM-based materials have been extensively utilized in optical devices, electrochemical/optical sensors, energy-related fields, and some other cutting-edge fields.…”