<br>pH 响应、逐层电荷反转纳米颗粒表面增强生物膜渗透和根除,ACS Biomaterials Science & Engineering

当前位置： X-MOL 学术 › ACS Biomater. Sci. Eng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

pH 响应、逐层电荷反转纳米颗粒表面增强生物膜渗透和根除
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-06-30 , DOI: 10.1021/acsbiomaterials.3c00481
Elad Deiss-Yehiely _{1,

2} , Gerardo Cárcamo-Oyarce ₃ , Adam G Berger _{2,

4,

5} , Katharina Ribbeck ₃ , Paula T Hammond _{2,

4,

6}

Affiliation

根深蒂固在生物膜内的微生物可以承受高浓度 1000 倍的抗生素，部分原因是粘性细胞外基质会隔离和减弱抗菌活性。与单独的游离药物相比，基于纳米颗粒 (NP) 的疗法可以帮助在整个生物膜中提供更高的局部浓度，从而提高疗效。规范的设计标准规定带正电荷的纳米颗粒可以多价结合阴离子生物膜成分并增加生物膜渗透。然而，阳离子颗粒是有毒的，并且会迅速从体内循环中清除，限制了它们的使用。因此，我们试图设计 pH 响应型纳米颗粒，将其表面电荷从负变为正，以响应生物膜 pH 微环境的降低。我们合成了一系列 pH 依赖性、可水解聚合物，并采用逐层 (LbL) 静电组装方法来制造以这些聚合物作为最外表面的生物相容性纳米粒子。 NP 电荷转化率由聚合物亲水性和侧链结构决定，在实验时间内从数小时到无法检测到。 LbL NP 具有越来越快的电荷转换率，更有效地渗透并在野生型 (PAO1) 和突变体过表达生物量 (Δ wspF )铜绿假单胞菌生物膜中积累。最后，妥布霉素（一种已知被阴离子生物膜成分捕获的抗生素）被加载到 LbL NP 的最后一层。与最慢的电荷转换器和游离妥布霉素相比，最快的电荷转换 NP 的 Δ wspF集落形成单位减少了 3.2 倍。这些研究为设计可响应基质相互作用的生物膜穿透纳米颗粒提供了一个框架，最终提高了抗菌药物的有效输送。

"点击查看英文标题和摘要"

pH-Responsive, Charge-Reversing Layer-by-Layer Nanoparticle Surfaces Enhance Biofilm Penetration and Eradication

Microbes entrenched within biofilms can withstand 1000-fold higher concentrations of antibiotics, in part due to the viscous extracellular matrix that sequesters and attenuates antimicrobial activity. Nanoparticle (NP)-based therapeutics can aid in delivering higher local concentrations throughout biofilms as compared to free drugs alone, thereby enhancing the efficacy. Canonical design criteria dictate that positively charged nanoparticles can multivalently bind to anionic biofilm components and increase biofilm penetration. However, cationic particles are toxic and are rapidly cleared from circulation in vivo, limiting their use. Therefore, we sought to design pH-responsive NPs that change their surface charge from negative to positive in response to the reduced biofilm pH microenvironment. We synthesized a family of pH-dependent, hydrolyzable polymers and employed the layer-by-layer (LbL) electrostatic assembly method to fabricate biocompatible NPs with these polymers as the outermost surface. The NP charge conversion rate, dictated by polymer hydrophilicity and the side-chain structure, ranged from hours to undetectable within the experimental timeframe. LbL NPs with an increasingly fast charge conversion rate more effectively penetrated through, and accumulated throughout, wildtype (PAO1) and mutant overexpressing biomass (ΔwspF) Pseudomonas aeruginosa biofilms. Finally, tobramycin, an antibiotic known to be trapped by anionic biofilm components, was loaded into the final layer of the LbL NP. There was a 3.2-fold reduction in ΔwspF colony forming units for the fastest charge-converting NP as compared to both the slowest charge converter and free tobramycin. These studies provide a framework for the design of biofilm-penetrating NPs that respond to matrix interactions, ultimately increasing the efficacious delivery of antimicrobials.

更新日期：2023-06-30

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南