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与抗CD22单克隆抗体偶联的载阿霉素血小板:一种用于淋巴瘤治疗且可避免心肺毒性的新型靶向递送系统

Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance.

作者信息

Xu Peipei, Zuo Huaqin, Zhou Rongfu, Wang Fan, Liu Xu, Ouyang Jian, Chen Bing

机构信息

Department of Hematology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, 210093, P. R. China.

出版信息

Oncotarget. 2017 Apr 6;8(35):58322-58337. doi: 10.18632/oncotarget.16871. eCollection 2017 Aug 29.

Abstract

B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs. Anti-CD22 mAb-labeled platelets can precisely deliver DOX to tumor cells. Our and experiments showed the enhanced antitumor activity and attenuated cardiotoxicity of DOX when delivered as DOX-platelet-CD22. Compared with other delivery systems, the uptake of DOX-platelet-CD22 by macrophage-like cells decreased. Moreover, DOX-platelet-CD22 showed platelet properties, such as tumor cell-induced platelet aggregation. Therefore, targeted chemotherapy that is mediated by DOX-platelet-CD22 is a promising option for lymphoma treatment.

摘要

B细胞淋巴瘤约占所有成人非霍奇金淋巴瘤病例的85%。阿霉素(DOX)是治疗非霍奇金淋巴瘤不可或缺的药物。然而,DOX会引起严重的心脏毒性,这限制了它在传统治疗策略中的应用。在本研究中,我们开发了一种用于淋巴瘤治疗的新型药物递送系统:负载DOX的血小板与抗CD22单克隆抗体(mAb)偶联(DOX-血小板-CD22)。血小板是具有生物相容性和免疫相容性的药物载体,能够延长药物的循环时间。抗CD22 mAb标记的血小板可以将DOX精确递送至肿瘤细胞。我们的……实验表明,以DOX-血小板-CD22形式递送时,DOX的抗肿瘤活性增强且心脏毒性减弱。与其他递送系统相比,巨噬细胞样细胞对DOX-血小板-CD22的摄取减少。此外,DOX-血小板-CD22表现出血小板特性,如肿瘤细胞诱导的血小板聚集。因此,由DOX-血小板-CD22介导的靶向化疗是淋巴瘤治疗的一个有前景的选择。 (注:原文中“Our and experiments”表述不完整,这里按原文翻译)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c196/5601655/56ed078b31f7/oncotarget-08-58322-g001.jpg

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