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首页> 外文期刊>Applied Microbiology and Biotechnology >A high-risk papillomavirus 18 E7 affibody-enabled in vivo imaging and targeted therapy of cervical cancer
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A high-risk papillomavirus 18 E7 affibody-enabled in vivo imaging and targeted therapy of cervical cancer

机译：高风险的乳头瘤病毒18 e7 Ablibody-Libodise在体内成像和宫颈癌的靶向治疗中

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摘要

High-risk papillomavirus (HPV) is one of the major reasons for cervical cancer, causing most lethal gynecologic malignancies worldwide. For cervical cancer progression, oncogene E7 plays vital roles and is used as one of the major targets for cervical tumor diagnosis and treatment. In the clinic, successful treatment of cervical cancer relies on diagnosing the disease at an early stage, where a late-stage diagnosis usually led to treatment failure. In this work, we designed and purified an HPV18 E7 oncogene targeting affibody, named as Z(HPV18E7), for in vitro and in vivo imaging and targeted treatment of cervical cancer. In vitro, Z(HPV18E7) showed a specific targeting effect against an HPV18 positive cell line; as a contrast, the affibody did not target the HPV18 negative cell line. In vivo, we tested the bio-distribution of the affibody in mice bearing cervical cancer. The whole animal imaging analysis indicated the affibody-targeted tumor tissue specifically with 10min after injection, and the affibody reached the highest level at tumor tissues 45min after injection. At the 24th hour after injection, the affibody still maintained a certain level in tumor tissues compared to other organs. To test the therapeutic effect of this affibody, we modified the affibody (i.e., Z(HPV18E7)) with a clinically used anti-cancer agent (i.e., Pseudomonas exotoxin). In a mice cervical cancer model, Z(HPV18E7) was able to deliver Pseudomonas exotoxin to tumor tissues effectively, showing great potential for cancer treatment. This study indicated that Z(HPV18E7) could be employed for in vitro imaging and targeted treatment of cervical cancer. Beyond the chemotherapeutic agent used in this work, the affibody could be extended for carrying other therapeutic agents for cervical cancer treatment.
机译：高风险乳头瘤病毒（HPV）是宫颈癌的主要原因之一，导致全世界大多数致命的妇科恶性肿瘤。对于宫颈癌进展，癌基因E7起到重要的作用，用作宫颈肿瘤诊断和治疗的主要目标之一。在临床中，成功治疗宫颈癌依赖于在早期阶段诊断疾病​​，其中晚期诊断通常导致治疗失败。在这项工作中，我们设计并纯化了HPV18 E7癌基因靶向隐语，其命名为Z（HPV18E7），用于体外和体内成像和针对宫颈癌的靶向治疗。体外，Z（HPV18E7）显示针对HPV18阳性细胞系的特异性靶向效果;作为对比度，亲吻没有靶向HPV18阴性细胞系。在体内，我们测试了患有宫颈癌小鼠的隐语的生物分布。整体动物成像分析表明注射后特别用10min的亲自靶向肿瘤组织，并在注射后45min达到肿瘤组织的最高水平。在注射后第24小时，与其他器官相比，亲吻仍然在肿瘤组织中保持一定水平。为了测试这种粘合的治疗效果，通过临床使用的抗癌剂（即，假单胞菌毒素）修饰了粘合剂（即，Z（HPV18E7））。在小鼠宫颈癌模型中，Z（HPV18E7）能够有效地向肿瘤组织提供假单胞菌以肿瘤组织，显示出巨大的癌症治疗潜力。该研究表明，Z（HPV18E7）可用于体外成像和宫颈癌的靶向治疗。除了在这项工作中使用的化学治疗剂之外，可以延长伴随宫颈癌治疗的其他治疗剂。

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