Aix Marseille Univ, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), UMR 7325, Equipe Labelisée Ligue Contre le Cancer, Parc Scientifique et Technologique de Luminy, Marseille, France.
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Nanoscale. 2022 Jul 7;14(26):9286-9296. doi: 10.1039/d2nr02305a.
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 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 dynamic self-assembly and offers a new perspective for combatting recalcitrant bacterial infection.
令人震惊且普遍存在的抗生素耐药性危机迫切需要创新的“非常规”抗菌剂，这些抗菌剂与传统抗生素有很大的不同。在这种情况下，我们已经基于由具有不同末端官能团的亲水性聚（酰胺-胺）树枝状大分子组成的两亲性树枝状大分子自组装的动态超分子树枝状纳米系统建立了抗菌候选物。值得注意的是，带有胺端基的两亲性树枝状大分子对革兰氏阳性菌、革兰氏阴性菌和耐药菌均表现出很强的抗菌活性，并能阻止生物膜的形成。结合实验方法和计算机建模的多学科研究表明，树枝状大分子与细菌膜通过静电相互作用相互作用和结合，在细菌膜中富集，然后动态自组装成超分子纳米组装体，以实现更强和多价相互作用。反过来，这又迅速将疏水性树枝状大分子尾巴插入细菌膜中，从而导致细菌细胞裂解，并构成强大的抗菌活性。我们的研究提出了一种基于动态自组装的创建基于纳米技术的抗菌候选物的新概念，并为对抗难治性细菌感染提供了新的视角。
