Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms
Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms
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动态自组装超分子树枝状聚合物纳米系统作为对抗耐药细菌和生物膜的有效抗菌候选物
DOI：
10.1039/d2nr02305a
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发表时间：
2022-06-01
期刊：
影响因子：
6.7
通讯作者：
Peng, Ling
中科院分区：
文献类型：
--
作者：
Dhumal, Dinesh;Maron, Bar;Peng, Ling
令人担忧且普遍存在的抗生素耐药性危机迫切需要创新的“开箱即用”抗菌剂，它与传统抗生素有很大不同。在这种背景下，我们建立了基于动态超分子树枝状大分子纳米系统的抗菌候选物，该纳米系统由两亲性树枝状大分子自组装而成，该两亲性树枝状大分子由长疏水性烷基链和具有不同末端功能的小亲水性聚（酰胺胺）树枝状大分子组成。值得注意的是，具有胺末端的两亲性树枝状大分子对革兰氏阳性菌、革兰氏阴性菌以及耐药菌均表现出很强的抗菌活性，并能防止生物膜的形成。结合实验方法和计算机建模的多学科研究表明，树枝状聚合物通过静电相互作用与细菌膜相互作用和结合，在细菌膜上它变得富集，然后动态自组装成超分子纳米组件，以实现更强的多价相互作用。这些反过来又迅速促进疏水性树枝状聚合物尾部插入细菌膜，从而诱导细菌细胞裂解并构成强大的抗菌活性。我们的研究提出了一种通过动态自组装创建基于纳米技术的抗菌候选物的新概念，并为对抗顽固性细菌感染提供了新的视角。
The alarming and prevailing antibiotic resistance crisis urgently calls for innovative "outside of the box" antibacterial agents, which can differ substantially from conventional antibiotics. In this context, we have established antibacterial candidates based on dynamic supramolecular dendrimer nanosystems self-assembled with amphiphilic dendrimers composed of a long hydrophobic alkyl chain and a small hydrophilic poly(amidoamine) dendron bearing distinct terminal functionalities. Remarkably, the amphiphilic dendrimer with amine terminals exhibited strong antibacterial activity against both Gram-positive and Gram-negative as well as drug-resistant bacteria, and prevented biofilm formation. Multidisciplinary studies combining experimental approaches and computer modelling together demonstrate that the dendrimer interacts and binds via electrostatic interactions with the bacterial membrane, where it becomes enriched and then dynamically self-assembles into supramolecular nanoassemblies for stronger and multivalent interactions. These, in turn, rapidly promote the insertion of the hydrophobic dendrimer tail into the bacterial membrane thereby inducing bacterial cell lysis and constituting powerful antibacterial activity. Our study presents a novel concept for creating nanotechnology-based antibacterial candidates via dynamic self-assembly and offers a new perspective for combatting recalcitrant bacterial infection.