Beyond the Charge: Interplay of Nanogels’ Functional Group and Zeta-Potential for Antifungal Drug Delivery to Human Pathogenic Fungus Aspergillus Fumigatus

IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Theresa Vogel, Simon Kohlmann, Zahraa Abboud, Sina Thusek, Franziska Fella, Joerg Teßmar, Kazuhisa Sekimizu, Atsushi Miyashita, Andreas Beilhack, Jürgen Groll, Yidong Yu, Krystyna Albrecht
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Abstract

The ubiquitous mold Aspergillus fumigatus (A. fumigatus) is one of the main fungal pathogens causing invasive infections in immunocompromised humans. Conventional antifungal agents exhibit limited efficacy and often cause severe side effects. Nanoparticle-based antifungal delivery provides a promising alternative, which can increase local drug concentration; while, mitigating toxicity, thereby enhancing treatment efficacy. Previous research underscores the potential of poly(glycidol)-based nanogels (NG) with negative surface charge as carriers for delivering antifungals to A. fumigatus hyphae. In this study, NG is tailored with 2-carboxyethyl acrylate (CEA) or with phosphoric acid 2-hydroxyethyl acrylate (PHA). It is discovered that quenching with PHA clearly improves the adhesion of NG to hyphal surface and the internalization of NG into the hyphae under protein-rich conditions, surpassing the outcomes of non-quenched and CEA-quenched NG. This enhancement cannot be solely attributed to an increase in negative surface charge but appears to be contingent on the functional group of the quencher. Further, it is demonstrated that itraconazole-loaded, PHA-functionalized nanogels (NGxPHA-ITZ) show lower MIC in vitro and superior therapeutic effect in vivo against A. fumigatus compared to pure itraconazole. This confirms NGxPHA as a promising antifungal delivery system.

Abstract Image

超越电荷:纳米凝胶的功能基团与 Zeta 电位在向人类致病真菌曲霉菌输送抗真菌药物中的相互作用。
无处不在的烟曲霉菌(A. fumigatus)是引起免疫力低下人群侵袭性感染的主要真菌病原体之一。传统的抗真菌剂疗效有限,而且往往会产生严重的副作用。基于纳米粒子的抗真菌给药技术提供了一种前景广阔的替代方案,既能提高局部药物浓度,又能减轻毒性,从而提高疗效。以往的研究强调了表面带负电荷的聚缩水甘油基纳米凝胶(NG)作为载体向烟曲霉菌丝输送抗真菌药物的潜力。在这项研究中,我们用 2-丙烯酸羧乙酯(CEA)或磷酸 2-丙烯酸羟乙酯(PHA)定制了 NG。我们发现,在富含蛋白质的条件下,用PHA淬火明显改善了NG与菌丝表面的粘附性以及NG在菌丝中的内化,超过了未淬火和CEA淬火NG的结果。这种增强不能完全归因于表面负电荷的增加,而似乎取决于淬灭剂的功能基团。此外,我们还证明,与纯伊曲康唑相比,负载了 PHA 功能化的伊曲康唑纳米凝胶(NGxPHA-ITZ)在体外的 MIC 更低,在体内对烟曲霉菌的治疗效果更好。这证实了 NGxPHA 是一种很有前景的抗真菌给药系统。本文受版权保护。保留所有权利。
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来源期刊
Macromolecular bioscience
Macromolecular bioscience 生物-材料科学:生物材料
CiteScore
7.90
自引率
2.20%
发文量
211
审稿时长
1.5 months
期刊介绍: Macromolecular Bioscience is a leading journal at the intersection of polymer and materials sciences with life science and medicine. With an Impact Factor of 2.895 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)), it is currently ranked among the top biomaterials and polymer journals. Macromolecular Bioscience offers an attractive mixture of high-quality Reviews, Feature Articles, Communications, and Full Papers. With average reviewing times below 30 days, publication times of 2.5 months and listing in all major indices, including Medline, Macromolecular Bioscience is the journal of choice for your best contributions at the intersection of polymer and life sciences.
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