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开发一种新型热敏感多功能脂质体,通过抗体连接靶向 EGFR 表达的肿瘤。

Development of a novel thermal-sensitive multifunctional liposome with antibody conjugation to target EGFR-expressing tumors.

机构信息

Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, Center For Intelligent Drug Systems and Smart Bio-devices (IDS(2)B), National Chiao Tung University, Hsinchu, Taiwan.

Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

出版信息

Nanomedicine. 2019 Jan;15(1):285-294. doi: 10.1016/j.nano.2018.10.006. Epub 2018 Nov 1.

Abstract

A novel EGFR-targeting, thermal-sensitive multifunctional liposome (TSML) was developed based on manganese-doped magnetism-engineered iron oxide nanoparticles (MnMEIOs) and gold nanorods (AuNRs) for efficient photothermal therapy and magnetic resonance (MR) imaging. An Erbitux-conjugated TSML (Erb-TSML) was encapsulated with doxorubicin and gold nanorods conjugated with manganese-doped magnetism-engineered iron oxide nanoparticles, for theranostic applications of EGFR-positive tumors. The Erb-TSML selectively targeted EGFR-positive tumors and promoted tumor destruction by laser activation. Using confocal microscopy, MR and optical imaging, we demonstrated that Erb-TSML specifically bound to A431 tumor cells. No signs of major morphological damages to the normal tissues were observed in mice treated with Erb-TSML and laser, indicating this theranostic platform protected heart against doxorubicin-induced toxicity to normal tissues. These results indicate that the Erb-TSML may be a promising diagnostic and therapeutic platform for EGFR-overexpressing tumors.

摘要

一种新型的 EGFR 靶向、热敏多功能脂质体(TSML)是基于锰掺杂磁工程氧化铁纳米粒子(MnMEIOs)和金纳米棒(AuNRs)开发的,用于高效的光热治疗和磁共振(MR)成像。一种 Erbitux 偶联的 TSML(Erb-TSML)封装了阿霉素和金纳米棒,金纳米棒上偶联了锰掺杂磁工程氧化铁纳米粒子,用于 EGFR 阳性肿瘤的治疗诊断应用。Erb-TSML 选择性地靶向 EGFR 阳性肿瘤,并通过激光激活促进肿瘤破坏。通过共聚焦显微镜、MR 和光学成像,我们证明了 Erb-TSML 特异性地与 A431 肿瘤细胞结合。在接受 Erb-TSML 和激光治疗的小鼠中,未观察到正常组织出现明显的形态损伤迹象,表明这种治疗诊断平台可保护心脏免受阿霉素对正常组织的毒性作用。这些结果表明,Erb-TSML 可能是一种有前途的诊断和治疗 EGFR 过表达肿瘤的平台。

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