Isolation of Tumour-Derived Extracellular Vesicles From the Plasma of Dogs Affected by Intracranial Tumours Showing Heterologous and Cross-Species Tropism: A Pilot Study.

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES
Veterinary and comparative oncology Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI:10.1111/vco.13016
Simona Vincenti, Alessandro Villa, Zemira de Mitri, Arianna Maiolini, Silvia Franzé, Daniela Schweizer, Anna Oevermann, Paolo Ciana
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Abstract

Canine and human brain tumours exhibit similar incidence rates and prognoses. Recent studies have demonstrated that extracellular vesicles derived from human patients (PDEVs) can be loaded with contrast agents and exhibit tumour tropism in murine models. We showed in a previous study that gadolinium-labelled EVs derived from canine gliomas (cPDEVs) can selectively targets murine glioblastoma cells in animal models. As a further step, we investigated the potential heterologous and cross-species tumour tropism of cPDEVs with brain tumours. With the perspective of imminent clinical application as both markers and drug delivery tools, we have successfully established the isolation protocol for cPDEVs and confirmed the aseptic conditions of the procedure and therefore the sterility of the isolated EVs. To assess the functionality of cPDEVs as drug delivery tool, they were loaded with indocyanine green (ICG) and injected into murine models of cancer for in vivo fluorescence biodistribution studies. Biodistribution analysis in mice revealed that ICG-loaded cPDEVs injected into murine models of subcutaneous tumours accumulated exclusively in the neoplastic tissue, even when evaluated 24 h post-injection, thus showing the cross-species and heterologous selective tumour tropism of the nanoparticles. With these tests, we have established a safe protocol for isolating and loading autologous cPDEVs with various markers, thereby paving the way for the clinical testing phase. These significant findings suggest the potential use of cPDEVs as a theranostic tool in the management of canine brain tumours, with promising implications for translational medicine applications in the future.

从受颅内肿瘤影响的犬血浆中分离肿瘤衍生的细胞外小泡,显示异源和跨物种趋向性:一项试点研究。
犬脑肿瘤和人类脑肿瘤的发病率和预后相似。最近的研究表明,从人类患者身上提取的细胞外囊泡(PDEVs)可以装载造影剂,并在小鼠模型中表现出肿瘤趋向性。我们在之前的一项研究中表明,从犬胶质瘤中提取的钆标记的细胞外小泡(cPDEVs)可以在动物模型中选择性地靶向小鼠胶质母细胞瘤细胞。我们进一步研究了 cPDEVs 对脑肿瘤的潜在异源和跨物种肿瘤滋养性。从即将作为标记物和给药工具应用于临床的角度出发,我们成功建立了 cPDEVs 的分离方案,并确认了该过程的无菌条件,从而保证了分离出的 EVs 的无菌性。为了评估 cPDEVs 作为药物递送工具的功能,我们将其装载吲哚菁绿(ICG)并注射到小鼠癌症模型中,进行体内荧光生物分布研究。对小鼠进行的生物分布分析表明,即使在注射后 24 小时进行评估,注入小鼠皮下肿瘤模型的含吲哚菁绿的 cPDEV 也只在肿瘤组织中蓄积,从而显示了纳米颗粒的跨物种和异源选择性肿瘤滋养特性。通过这些测试,我们建立了分离自体 cPDEV 并将其装入各种标记物的安全方案,从而为临床测试阶段铺平了道路。这些重要发现表明,cPDEVs 有可能作为一种治疗工具用于犬脑肿瘤的治疗,这对未来转化医学的应用具有广阔的前景。
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来源期刊
Veterinary and comparative oncology
Veterinary and comparative oncology 农林科学-兽医学
CiteScore
4.80
自引率
9.50%
发文量
75
审稿时长
>24 weeks
期刊介绍: Veterinary and Comparative Oncology (VCO) is an international, peer-reviewed journal integrating clinical and scientific information from a variety of related disciplines and from worldwide sources for all veterinary oncologists and cancer researchers concerned with aetiology, diagnosis and clinical course of cancer in domestic animals and its prevention. With the ultimate aim of diminishing suffering from cancer, the journal supports the transfer of knowledge in all aspects of veterinary oncology, from the application of new laboratory technology to cancer prevention, early detection, diagnosis and therapy. In addition to original articles, the journal publishes solicited editorials, review articles, commentary, correspondence and abstracts from the published literature. Accordingly, studies describing laboratory work performed exclusively in purpose-bred domestic animals (e.g. dogs, cats, horses) will not be considered.
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