Ofloxacin@Doxorubicin-Epirubicin functionalized MCM-41 mesoporous silica-based nanocarriers as synergistic drug delivery tools for cancer related bacterial infections
Ofloxacin@Doxorubicin-Epirubicin functionalized MCM-41 mesoporous silica-based nanocarriers as synergistic drug delivery tools for cancer related bacterial infections
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DOI：
10.1016/j.bioorg.2021.105470
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发表时间：
2022-01-01
影响因子：
5.1
通讯作者：
Oliveira, Elisabete
中科院分区：
文献类型：
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作者：
Galhano, Joana;Marcelo, Goncalo A.;Oliveira, Elisabete
介孔二氧化硅纳米颗粒（MN）成为新的有前途的药物输送平台，能够克服细菌的耐药性。利用纳米颗粒和药物之间的协同相互作用，将药物双重装载在这些纳米载体上，可以被认为是一种即使在非常低的浓度下也具有积极作用的提高对耐药细菌的功效的方法。考虑到癌症患者对几乎任何类型的细菌感染都非常敏感，在这项工作中，合成了基于介孔二氧化硅的纳米载体MN和MN @EPI，并进行了单和/或双负载抗生素（氧氟沙星- OFLO）和抗癌药物（阿霉素- DOX;研究了它们对大肠杆菌、金黄色葡萄球菌、耐甲氧西林葡萄球菌的抗菌活性。金黄色葡萄球菌（MRSA）、粪肠球菌和铜绿假单胞菌。含有氧氟沙星的制剂如MNs-OFLO、MNs-EPI + OFLO、MNs-DOX + OFLO和MNs@EPI + OFLO在所有测试的细菌菌株中呈现抗菌活性。所有这些在大肠杆菌中更有效，MNs-OFLO、MNs-EPI + OFLO和MNs-DOX + OFLO的MIC和MBC值约为1和2 μ g纳米材料/mL，分别对应于0.03、0.02和0.04 μ g/mL的氧氟沙星浓度。在鸡尾酒制剂中，与单氧氟沙星系统相比，表阿霉素与氧氟沙星的缀合呈现出更有效的抗菌活性，氧氟沙星浓度降低超过3倍。到目前为止，对于其中表阿霉素在纳米颗粒表面官能化的系统（MN @EPI）获得了最有效的协同效应，其中与MNs-OFLO和MNs-EPI + OFLO系统相比，在铜绿假单胞菌中分别获得了40倍和33倍的氧氟沙星浓度降低。这些影响在所有测试的细菌菌株中显示，甚至在具有获得性耐药机制的菌株中，例如MRSA。
Mesoporous silica nanoparticles (MNs) emerged as new promising drug-delivery platforms capable to overcome resistance in bacteria. Dual loading of drugs on these nanocarriers, exploiting synergistic interactions between the nanoparticles and the drugs, could be considered as a way to increase the efficacy against resistant bacteria with a positive effect even at very low concentrations. Considering that patients with cancer are highly susceptible to almost any type of bacterial infections, in this work, nanocarriers mesoporous silica-based, MNs and MNs@EPI were synthetized and submitted to single and/or dual loading of antibiotics (ofloxacin - OFLO) and anticancer drugs (Doxorubicin - DOX; Epirubicin - EPI), and investigated regarding their antibacterial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis and Pseudomonas aeruginosa. Formulations containing ofloxacin such as MNs-OFLO, MNs-EPI + OFLO, MNs-DOX + OFLO and MNs@EPI + OFLO, present antibacterial activity in all bacterial strains tested. All these are more effective in E.coli with MIC and MBC values for MNs-OFLO, MNs-EPI + OFLO and MNs-DOX + OFLO of around 1 and 2 mu gnanomaterial/mL, corresponding to ofloxacin concentrations of 0.03, 0.02 and 0.04 mu g/mL, respectively. In the cocktail formulations the conjugation of epirubicin with ofloxacin presents a more effective antibacterial activity with more than 3-fold reduction of ofloxacin concentration when comparing to the single ofloxacin system. By far, the most effective synergistic effect was obtained for the system where epirubicin was functionalized at nanoparticles surface (MNs@EPI), where a 40-fold and 33-fold reductions of ofloxacin concentration were obtained, in P. aeruginosa in comparison to the MNs-OFLO and MNs-EPI + OFLO systems, respectively. These effects are shown in all bacterial strains tested, even in strains that have acquired resistance mechanisms, such as MRSA.