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

// Peipei Xu 1, * , Huaqin Zuo 1, * , Rongfu Zhou 1 , Fan Wang 1 , Xu Liu 1 , Jian Ouyang 1 and Bing Chen 1 1 Department of Hematology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, 210093, P. R. China * Co-first author Correspondence to: Peipei Xu, email: xu_peipei0618@163.com Jian Ouyang, email: ouyangj211@163.com Bing Chen, email: chenb211@163.com Keywords: platelet, anti-CD22 mAbs, doxorubicin, drug delivery system, lymphoma Received: October 24, 2016 Accepted: March 14, 2017 Published: April 06, 2017 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 in vitro and in vivo 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.