Antimicrobial peptides that target the integrity of bacterial envelopes can eradicate pathogens with little development of resistance, but they often inflict nonselective toxicity toward mammalian cells. The prevailing approach to optimize the selectivity of cationic peptides has been to modify their composition. Instead, we invent a new generation of broad-spectrum antibacterial nanoconstructs with negligible mammalian cell toxicity through a competitive displacement of counter polyanions from the complementary polycations. The nanoconstruct, which has a highly cationic Au nanoparticles (NPs) core shielded by polymeric counterions, is inert in nonbacterial environments. When exposed to negatively charged bacterial envelopes, this construct sheds its polyanions, triggering a cationic Au NP/bacterial membrane interaction that rapidly kills Gram-positive and Gram-negative bacteria. The anionic charge and hydrophilicity of the polyanion provides charge neutralization for the peptide-decorated Au NP core, but it is also bacteria-displaceable. These results provide a foundation for the development of other cationic particles and polymeric counterion combinations with potent antimicrobial activity without toxicity.

中文翻译：

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细菌可置换聚合物抗衡离子的无毒抗菌阳离子肽纳米结构。

靶向细菌包膜完整性的抗菌肽可以根除几乎没有耐药性的病原体，但它们通常会对哺乳动物细胞产生非选择性毒性。优化阳离子肽选择性的主要方法是改变其组成。相反，我们发明了一种新型的广谱抗菌纳米结构，可通过竞争性地将互补聚阳离子中的反聚阴离子竞争性置换，从而使哺乳动物细胞毒性微不足道。纳米结构具有高度阳离子性的Au纳米颗粒（NPs）核心，被聚合物抗衡离子屏蔽，在非细菌环境中呈惰性。当暴露于带负电荷的细菌包膜时，该结构会脱落其聚阴离子，引发阳离子Au NP /细菌膜相互作用，从而迅速杀死革兰氏阳性和革兰氏阴性细菌。聚阴离子的阴离子电荷和亲水性为肽修饰的Au NP核提供电荷中和作用，但它也可被细菌置换。这些结果为开发具有有效抗微生物活性且无毒性的其他阳离子颗粒和高分子抗衡离子组合奠定了基础。