研究磁小体的药代动力学和免疫原性。

IF 4.5 3区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Artificial Cells, Nanomedicine, and Biotechnology Pub Date : 2024-12-01 Epub Date: 2024-01-12 DOI:10.1080/21691401.2023.2289367
M Haripriyaa, K Suthindhiran
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引用次数: 0

摘要

磁小体是一种氧化铁或硫化铁纳米大小的颗粒,周围有一层脂质双分子层,由一组被称为趋磁细菌(MTB)的细菌合成。磁小体已成为生物医学应用的一种有前途的候选物质,并有可能用作药物载体。然而,磁小体的药代动力学和免疫原性尚不清楚,因此无法应用于临床。在此,我们研究了磁小体的药代动力学,包括吸收、分布、代谢和消除(ADME)及其在体外和体内的免疫原性。磁小体与异硫氰酸荧光素(Mag-FITC)共轭,通过荧光显微镜确认其共轭情况,并利用流式细胞术分析评估其在 HeLa 细胞系中的吸收情况。结果显示,在 200 微克/毫升的浓度下,细胞吸收率最高可达 97%。此外,以 BALB/c 小鼠为研究对象,通过生物成像系统对 Mag-FITC 在体内不同时间间隔的生物分布进行了研究。Mag-FITC 既不会导致小鼠死亡,也不会造成小鼠身体不适,而且在注射 36 小时后,Mag-FITC 就会被消除,只留下微弱的浓度。对新陈代谢和消除分析进行了评估,以检测铁超载情况,结果显示,磁小体在 48 小时内被完全代谢掉。此外,组织病理学和血清分析表明,磁小体没有任何组织损伤,也没有任何异常的生化指标。这些结果支持了我们的研究,即磁小体在 48 小时的时间间隔内完全从血液循环中清除。此外,免疫原性分析表明,磁小体不会诱发任何炎症,通过间接酶联免疫吸附法估算的 IL 1β、IL 2、IL 6、IL 8、IFN γ 和 TNF α 等免疫标志物的峰值降低就表明了这一点。动物表现正常,任何器官均无急性或慢性毒性,这表明注射磁小体是安全的。这表明磁小体对生物系统是无害的,可用于有益的生物医学应用。因此,这项研究将促进对磁小体的了解和临床应用。
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Investigation of pharmacokinetics and immunogenicity of magnetosomes.

Magnetosomes are iron oxide or iron sulphide nano-sized particles surrounded by a lipid bilayer synthesised by a group of bacteria known as magnetotactic bacteria (MTB). Magnetosomes have become a promising candidate for biomedical applications and could be potentially used as a drug-carrier. However, pharmacokinetics and immunogenicity of the magnetosomes have not been understood yet which preclude its clinical applications. Herein, we investigated the pharmacokinetics of magnetosomes including Absorption, Distribution, Metabolism, and Elimination (ADME) along with its immunogenicity in vitro and in vivo. The magnetosomes were conjugated with fluorescein isothiocyanate (Mag-FITC) and their conjugation was confirmed through fluorescence microscopy and its absorption in HeLa cell lines was evaluated using flow cytometry analysis. The results revealed a maximum cell uptake of 97% at 200 µg/mL concentration. Further, the biodistribution of Mag-FITC was investigated in vivo by a bioimaging system using BALB/c mice as a subject at different time intervals. The Mag-FITC neither induced death nor physical distress and the same was eliminated post 36 h of injection with meagre intensities left behind. The metabolism and elimination analysis were assessed to detect the iron overload which revealed that magnetosomes were entirely metabolised within 48-h interval. Furthermore, the histopathology and serum analysis reveal no histological damage with the absence of any abnormal biochemical parameters. The results support our study that magnetosomes were completely removed from the blood circulation within 48-h time interval. Moreover, the immunogenicity analysis has shown that magnetosomes do not induce any inflammation as indicated by reduced peaks of immune markers such as IL 1β, IL 2, IL 6, IL8, IFN γ, and TNF α estimated through Indirect ELISA. The normal behaviour of animals with the absence of acute or chronic toxicities in any organs declares that magnetosomes are safe to be injected. This shows that magnetosomes are benign for biological systems enrouting towards beneficial biomedical applications. Therefore, this study will advance the understanding and application of magnetosomes for clinical purposes.

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来源期刊
Artificial Cells, Nanomedicine, and Biotechnology
Artificial Cells, Nanomedicine, and Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ENGINEERING, BIOMEDICAL
CiteScore
10.90
自引率
0.00%
发文量
48
审稿时长
20 weeks
期刊介绍: Artificial Cells, Nanomedicine and Biotechnology covers the frontiers of interdisciplinary research and application, combining artificial cells, nanotechnology, nanobiotechnology, biotechnology, molecular biology, bioencapsulation, novel carriers, stem cells and tissue engineering. Emphasis is on basic research, applied research, and clinical and industrial applications of the following topics:artificial cellsblood substitutes and oxygen therapeuticsnanotechnology, nanobiotecnology, nanomedicinetissue engineeringstem cellsbioencapsulationmicroencapsulation and nanoencapsulationmicroparticles and nanoparticlesliposomescell therapy and gene therapyenzyme therapydrug delivery systemsbiodegradable and biocompatible polymers for scaffolds and carriersbiosensorsimmobilized enzymes and their usesother biotechnological and nanobiotechnological approachesRapid progress in modern research cannot be carried out in isolation and is based on the combined use of the different novel approaches. The interdisciplinary research involving novel approaches, as discussed above, has revolutionized this field resulting in rapid developments. This journal serves to bring these different, modern and futuristic approaches together for the academic, clinical and industrial communities to allow for even greater developments of this highly interdisciplinary area.
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