Versatility of targeted antibiotic-loaded gold nanoconstructs for the treatment of biofilm-associated bacterial infections.
Versatility of targeted antibiotic-loaded gold nanoconstructs for the treatment of biofilm-associated bacterial infections.
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DOI：
10.1080/02656736.2017.1392047
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Smeltzer MS
中科院分区：
文献类型：
--
作者：
Meeker DG;Wang T;Harrington WN;Zharov VP;Johnson SA;Jenkins SV;Oyibo SE;Walker CM;Mills WB;Shirtliff ME;Beenken KE;Chen J;Smeltzer MS
我们先前证明了采用负载有光敏剂的抗体缀合的聚多巴胺（PDA）涂覆的金纳米笼（AuNC）的光活化治疗方法可用于协同杀死生物膜内的细菌细胞。使用对葡萄球菌蛋白A（Spa）具有特异性的抗体和对革兰氏阳性球菌（包括耐甲氧西林链球菌）具有活性的抗生素（达托霉素）对金黄色葡萄球菌进行了重点验证。金黄色葡萄球菌（MRSA）。然而，这种方法的一个重要方面是其潜在的治疗多功能性。在本报告中，我们通过检查用靶向S的替代抗体和抗生素产生的AuNC制剂的功效来评估这种多功能性。金黄色葡萄球菌和针对革兰氏阴性病原体铜绿假单胞菌的替代组合。结果证实，负载达托霉素的AuNC与靶向两种不同S.金黄色葡萄球菌脂蛋白（SACOL0486和SACOL0688）也有效地杀死生物膜环境中的MRSA。然而，我们的研究结果也表明抗生素的选择至关重要。具体地，发现与抗Spa抗体缀合的头孢洛林和万古霉素负载的AuNC相对于与相同抗体缀合的达托霉素负载的AuNC表现出降低的功效。相比之下，与靶向保守外膜蛋白的抗体缀合的负载庆大霉素的AuNC对铜绿假单胞菌生物膜高度有效。这些结果证实了我们方法的治疗多功能性。然而，就其协同功效依赖于实现致死光热效应和足够量的抗生素的热控制释放的能力而言，它们还证明了仔细设计适当的抗体和抗生素组合以实现所需的治疗协同作用的重要性。
We previously demonstrated that a photoactivatable therapeutic approach employing antibiotic-loaded, antibody-conjugated, polydopamine (PDA)-coated gold nanocages (AuNCs) could be used for the synergistic killing of bacterial cells within a biofilm. The approach was validated with a focus on Staphylococcus aureus using an antibody specific for staphylococcal protein A (Spa) and an antibiotic (daptomycin) active against Gram-positive cocci including methicillin-resistant S. aureus (MRSA). However, an important aspect of this approach is its potential therapeutic versatility. In this report, we evaluated this versatility by examining the efficacy of AuNC formulations generated with alternative antibodies and antibiotics targeting S. aureus and alternative combinations targeting the Gram-negative pathogen Pseudomonas aeruginosa. The results confirmed that daptomycin-loaded AuNCs conjugated to antibodies targeting two different S. aureus lipoproteins (SACOL0486 and SACOL0688) also effectively kill MRSA in the context of a biofilm. However, our results also demonstrate that antibiotic choice is critical. Specifically, ceftaroline and vancomycin-loaded AuNCs conjugated to anti-Spa antibodies were found to exhibit reduced efficacy relative to daptomycin-loaded AuNCs conjugated to the same antibody. In contrast, gentamicin-loaded AuNCs conjugated to an antibody targeting a conserved outer membrane protein were highly effective against P. aeruginosa biofilms. These results confirm the therapeutic versatility of our approach. However, to the extent that its synergistic efficacy is dependent on the ability to achieve both a lethal photothermal effect and the thermally-controlled release of a sufficient amount of antibiotic, they also demonstrate the importance of carefully designing appropriate antibody and antibiotic combinations to achieve the desired therapeutic synergy.
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影响因子：
3.7
作者：
Galanzha EI;Shashkov E;Sarimollaoglu M;Beenken KE;Basnakian AG;Shirtliff ME;Kim JW;Smeltzer MS;Zharov VP
通讯作者：
Zharov VP
DOI：
10.1016/j.ijantimicag.2005.08.016
发表时间：
2005-12
影响因子：
10.8
作者：
Hsueh PR;Chen WH;Luh KT
通讯作者：
Luh KT
影响因子：
19
作者：
Chen J;Yang M;Zhang Q;Cho EC;Cobley CM;Kim C;Glaus C;Wang LV;Welch MJ;Xia Y
通讯作者：
Xia Y
影响因子：
3.7
作者：
Falagas ME;Bliziotis IA;Kasiakou SK;Samonis G;Athanassopoulou P;Michalopoulos A
通讯作者：
Michalopoulos A
影响因子：
3.1
作者：
Beenken, KE;Blevins, JS;Smeltzer, MS
通讯作者：
Smeltzer, MS