This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named “nanoantibiotics”, are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVO-loaded MSNs. After physicochemical characterization of this nanoantibiotic, the release kinetics of LEVO and the antimicrobial efficacy of each released dosage were evaluated. Besides, internalization studies of the MSNs functionalized with the G3 dendrimer were carried out, showing a high penetrability throughout Gram-negative bacterial membranes. This work evidences that the synergistic combination of polycationic dendrimers as bacterial membrane permeabilization agents with LEVO-loaded MSNs triggers an efficient antimicrobial effect on Gram-negative bacterial biofilm. These positive results open up very promising expectations for their potential application in new infection therapies.

Statement of significance

Seeking new alternatives to current available treatments of bacterial infections represents a great challenge in nanomedicine. This work reports the design and optimization of a new class of antimicrobial agent, named “nanoantibiotic”, based on mesoporous silica nanoparticles (MSNs) decorated with polypropyleneimine dendrimers of third generation (G3) and loaded with levofloxacin (LEVO) antibiotic. The covalently grafting of these G3 dendrimers to MSNs allows an effective internalization in Gram-negative bacteria. Furthermore, the LEVO loaded into the mesoporous cavities is released in a sustained manner at effective antimicrobial dosages. The novelty and originality of this manuscript relies on proving that the synergistic combination of bacteria-targeting and antimicrobial agents into a unique nanosystem provokes a remarkable antimicrobial effect against bacterial biofilm.

中文翻译：

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聚阳离子树枝状聚合物修饰的介孔二氧化硅纳米颗粒用于感染治疗

这项工作旨在通过使用载有能够穿透细菌壁的抗生素的纳米载体，从而提供一种有效且新颖的治疗感染的解决方案，从而提高抗菌效果。这些被称为“纳米抗生素”的纳米系统由介孔二氧化硅纳米颗粒（MSN）组成，该颗粒充当位于介孔内部的抗菌剂（左氧氟沙星，LEVO）的纳米载体。为了提供细菌膜相互作用能力的纳米系统，将聚阳离子树状聚合物，具体而言是第三代（G3）的聚（丙烯亚胺）树状聚合物共价接枝到LEVO负载的MSN的外表面。在对该纳米抗生素进行理化表征后，评估了LEVO的释放动力学和每种释放剂量的抗菌功效。除了，进行了用G3树状大分子官能化的MSN的内在化研究，结果表明在整个革兰氏阴性细菌膜中都具有很高的渗透性。这项工作证明聚阳离子树状大分子作为细菌膜通透剂与LEVO负载的MSN的协同组合可触发对革兰氏阴性细菌生物膜的有效抗菌作用。这些积极的结果为它们在新的感染治疗中的潜在应用打开了非常有希望的期望。这项工作证明聚阳离子树状大分子作为细菌膜通透剂与LEVO负载的MSN的协同组合可触发对革兰氏阴性细菌生物膜的有效抗菌作用。这些积极的结果为它们在新的感染治疗中的潜在应用打开了非常有希望的期望。这项工作证明聚阳离子树状大分子作为细菌膜通透剂与LEVO负载的MSN的协同组合可触发对革兰氏阴性细菌生物膜的有效抗菌作用。这些积极的结果为它们在新的感染治疗中的潜在应用打开了非常有希望的期望。

重要声明

在目前的细菌感染治疗方法中寻求新的替代方法代表了纳米医学的巨大挑战。这项工作报告了一种新型抗菌剂，称为“纳米抗生素”的设计和优化，该抗菌剂基于介孔二氧化硅纳米颗粒（MSN），该纳米颗粒装饰有第三代（G3）的聚丙烯亚胺树状大分子并负载有左氧氟沙星（LEVO）抗生素。这些G3树状聚合物的共价接枝到MSNs允许革兰氏阴性细菌的有效内在化。此外，加载到中孔腔中的LEVO以有效的抗菌剂量持续释放。