Long-Circulating Nanoemulsion with Oxygen and Drug Co-Delivery for Potent Photodynamic/Antibiotic Therapy Against Multidrug-Resistant Gram-Negative Bacterial Infection.

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S477278
Xiaolong Li, Xinyi Hou, Siqin Zhang, Jianming Xiong, Yuanyuan Li, Wenjun Miao
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引用次数: 0

Abstract

Purpose: Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES).

Methods: To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against Acinetobacter baumannii (A. baumannii) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo.

Results: ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL-1 of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating A. baumannii-induced acute peritonitis, accompanied by good biocompatibility in vivo.

Conclusion: Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.

长循环纳米乳液与氧气和药物共同输送,用于针对耐多药革兰氏阴性细菌感染的强效光动力/抗生素疗法
目的:与传统的光动力疗法(PDT)相比,给氧 PDT 是一种治疗耐多药(MDR)革兰氏阴性菌感染的有前途的策略,因为它能增强对细菌的敏化能力并扩大疗效。在过去的十年中,已经开发出了多种氧气和光敏剂联合输送的纳米平台。然而,它们在治疗感染性疾病方面的应用却因稳定性差和容易被网状内皮系统(RES)清除而受到阻碍:为了解决这些障碍,我们报道了一种含有氯素 e6(Ce6)和全氟碳化物(FDC)的红细胞膜(EM)伪装纳米乳液,命名为 ECF,显示出良好的胶体稳定性和长循环潜力,使其适用于对抗 MDR 革兰氏阴性细菌感染。该纳米乳液已制备完成并进行了表征。评估了ECF的载氧和释放性能、光动力活性以及对鲍曼不动杆菌(A. baumannii)的杀菌性能。此外,还使用 Raw 264.7 细胞在体外测试了其抗吞噬能力。此外,还研究了 ECF 在体内的药代动力学行为和治疗效率:结果:ECF 表现出卓越的氧气负载和释放性能、强大的光动力活性以及对哺乳动物细胞可忽略不计的毒性。此外,ECF 还能有效抑制吞噬细胞的摄取,静脉注射后在血液中的循环时间是未经电磁修饰的纳米乳液(CF)的 1.5 倍。此外,预氧-ECF 与抗生素和光照射相结合,对治疗鲍曼不动杆菌诱发的急性腹膜炎有显著疗效,而且在体内具有良好的生物相容性:结论:我们的研究结果提供了一种新的范例,可用于避开免疫清除、延长保留时间并提高协同杀菌能力,从而与光动力疗法和抗生素疗法相结合,治疗浮游细菌和革兰氏阴性菌感染。
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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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