Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France.
Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France.
ACS Nano. 2019 Apr 23;13(4):3992-4007. doi: 10.1021/acsnano.8b07902. Epub 2019 Mar 8.
Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB.
耐多药结核病（TB）是一个主要的公共卫生问题，每年涉及约 50 万例病例。患者很难坚持目前由超过 10000 片药物组成的严格治疗方案，治疗时间长达 2 年。因此，非常需要高效和配方更好的药物。我们之前已经表明，交联聚β-环糊精（pβCD）制成的纳米颗粒是将抗结核药物强效组合递送至肺部的有效载体。在这里，我们报告称，除了作为有效的药物载体外，pβCD 纳米颗粒还具有内在的抗菌特性。空的 pβCD 纳米颗粒在经肺部给药后能够损害小鼠肺部的结核分枝杆菌（Mtb）定植。pβCD 通过干扰脂筏来阻碍 Mtb 对巨噬细胞的定殖，而不会引起毒性。此外，pβCD 会引发巨噬细胞凋亡，导致受感染细胞耗竭，从而在肺部创造一个不利于 Mtb 持续存在的微环境。总之，我们的研究结果表明，负载或不负载抗生素的 pβCD 纳米颗粒本身具有抗菌作用，并可作为治疗结核病的药物方案制剂中的载体。
