Development and evaluation of cell membrane-based biomimetic nanoparticles loaded by Clostridium perfringens epsilon toxin: a novel vaccine delivery platform for Clostridial-associated diseases.

IF 3.6 3区 医学 Q3 NANOSCIENCE & NANOTECHNOLOGY Nanotoxicology Pub Date : 2023-06-01 Epub Date: 2023-09-11 DOI:10.1080/17435390.2023.2252899
Mokarameh Pudineh Moarref, Mojtaba Alimolaei, Tara Emami, Mohammad Kazem Koohi
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Abstract

As Clostridium perfringens (C. perfringens) epsilon toxin (ETX) ranks as the third most potent clostridial toxin after botulinum and tetanus toxins, vaccination is necessary for creatures that can be affected by it to be safe from the effects of this toxin. Nowadays, nanostructures are good choices for carriers for biological environments. We aimed to synthesize biomimetic biodegradable nanodevices to enhance the efficiency of the ETX vaccine. For this purpose, poly(lactic-co-glycolic acid) (PLGA) copolymer loaded with purified epsilon protoxin (proETX) to create nanoparticles called nanotoxins (NTs) and then coated by RBC membrane-derived vesicles (RVs) to form epsilon nanotoxoids (RV-NTs). The resulting RV-NTs shaped smooth spherical surfaces with double-layer core/shell structure with an average particle size of 105.9 ± 35.1 nm and encapsulation efficiency of 97.5% ± 0.13%. Compared with NTs, the RV-NTs were more stable for 15 consecutive days. In addition, although both structures showed a long-term cumulative release, the release rates from RV-NTs were slower than NTs during 144 hours. According to the results of cell viability, ETX loading in PLGA and entrapment in the RBC membrane decreased the toxicity of the toxin. The presence of PLGA enhances the uptake of proETX, and the synthesized structures showed no significant lesion after injection. These results demonstrate that NTs and RV-NTs could serve as an effective vaccine platform to deliver ETX for future in vivo assays.

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产气荚膜梭状芽孢杆菌epsilon毒素负载的基于细胞膜的仿生纳米颗粒的开发和评估:一种用于梭菌相关疾病的新型疫苗递送平台。
由于产气荚膜梭菌(C.perfringens)ε毒素(ETX)是仅次于肉毒杆菌和破伤风毒素的第三大梭菌毒素,因此有必要接种疫苗,使受其影响的生物免受这种毒素的影响。如今,纳米结构是用于生物环境的载体的良好选择。我们旨在合成仿生可生物降解的纳米器件,以提高ETX疫苗的效率。为此,聚乳酸-乙醇酸(PLGA)共聚物负载纯化的ε-原毒素(proETX)以产生称为纳米毒素(NT)的纳米颗粒,然后用红细胞膜衍生的囊泡(RV)包被以形成ε-纳米类毒素(RV NT)。所得RV NT形成光滑的球形表面,具有双层核/壳结构,平均粒径为105.9±35.1 nm,包封率为97.5%±0.13%。与NTs相比,RV NTs连续15天更稳定。此外,尽管两种结构都显示出长期累积释放,但在144期间,RV NT的释放速率低于NT 小时。根据细胞活力的结果,ETX在PLGA中的负载和在RBC膜中的包埋降低了毒素的毒性。PLGA的存在增强了proETX的摄取,并且合成的结构在注射后没有显示出显著的损伤。这些结果表明,NTs和RV NTs可以作为一种有效的疫苗平台,为未来的体内测定提供ETX。
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来源期刊
Nanotoxicology
Nanotoxicology 医学-毒理学
CiteScore
10.10
自引率
4.00%
发文量
45
审稿时长
3.5 months
期刊介绍: Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology . While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.
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