ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
DOTA-grafted Cationic Polymers Behaving as Powerful Macromolecular Resistance-reversal Agents (MRRAs) Combating Against New Delhi Metallo-β-lactamase (NDM)-producing Bacteria.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
New Delhi metallo-β-lactamase (NDM)-producing bacteria have posed a significant threat to human health. To navigate this tricky problem, numerous NDM inhibitors have been explored, showing great antibacterial synergy. But there are still be some problems to be tackled, such as suboptimal efficacy, rapid resistance evolution, and high cytotoxicity. Herein, we engineer two macromolecular resistance-reversal agents (MRRAs) via pharmacophore integration: linear (MRRAL) and nanostructured (MRRAN) topologies, both coordinating metal ion chelator-DOTA motif into tunable polycationic scaffolds. And we validate their efficacy through 4 clinically isolated NDM-producing pathogens. MRRAs present excellent effect boosting meropenem (MEM) to fight against those superbugs with the fractional inhibitory concentration indices much less than 0.5. Notably, the nanostructured MRRAN exhibited superior potency compared to its linear counterpart MRRAL under the same concentration of the active group of "DOTA." Mechanistic studies revealed that MRRAN could achieve bacterial membrane targeting through charge-mediated accumulation, exerting triple-action synergistic mechanisms: 1) physical membrane disruption through powerful local cationic surface interactions and hydrophobic force, 2) precise Zn
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