CD20 monoclonal antibody targeted nanoscale drug delivery system for doxorubicin chemotherapy: an in vitro study of cell lysis of CD20-positive Raji cells

Abstract

Shuang Jiang,1,2,* Xiaobo Wang,2,* Zhiran Zhang,2 Lan Sun,3 Yunzhu Pu,3 Hongjuan Yao,3 Jingcao Li,3 Yan Liu,3 Yingge Zhang,3 Weijing Zhang1,4 1Department of Lymphoma, Affiliated Hospital of the Military Medical Academy of Sciences, Beijing, 2Department of Pharmacy, 210th Hospital of the People’s Liberation Army, Dalian, 3Key Laboratory of Nanopharmacology and Nanotoxicology, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 4Department of Lymphoma, Beijing Shijitan Hospital of Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: A monoclonal antibody targeted nanoscale drug delivery system (NDDS) for chemotherapy was evaluated in CD20-positive Raji cells in vitro. Nanoparticles were formed by the assembly of an amphiphilic polymer consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypolyethyleneglycol-2000 (DSPE-PEG2000). Active carbon nanoparticles (ACNP) were conjugated to the chemotherapeutic agent, doxorubicin (DOX), and the nanoliposome carrier, DSPE-PEG2000 and DSPE-PEG2000-NH2 conjugated to the human anti-CD20 monoclonal antibody that targets B-lymphocytes. This monoclonal antibody targeted nanoparticle delivery system for chemotherapy formed the active NDDS complex, ACNP-DOX-DSPE-PEG2000-anti-CD20. This active NDDS was spherical in morphology and had good dispersion in the culture medium. When compared with the effects on CD20-negative YTS cells derived from natural killer/T-cell lymphoma, the active NDDS, ACNP-DOX-DSPE-PEG2000-anti-CD20, demonstrated DOX delivery to CD20-positive Raji cells derived from Burkitt’s lymphoma (B cell lymphoma), resulting in increased cell killing in vitro. The intracellular targeting efficiency of the ACNP-DOX-DSPE-PEG2000-anti-CD20 complex was assessed by confocal laser microscopy and flow cytometry. The findings of this in vitro study have shown that the DSPE-PEG2000 polymeric liposome is an effective nanocarrier of both a monoclonal antibody and a chemotherapy agent and can be used to target chemotherapy to specific cells, in this case to CD20-positive B-cells. Future developments in this form of targeted therapy will depend on the development of monoclonal antibodies that are specific for malignant cells, including antibodies that can distinguish between lymphoma cells and normal lymphocyte subsets. Keywords: CD20, active carbon nanoparticles, doxorubicin, nanoscale drug delivery, targeted therapy, DSPE-NH2-anti-CD20 conjugate

Keywords

• CD20
• active carbon nanoparticles
• doxorubicin
• nanoscale drug delivery
• targeted therapy