Modular design of Bi-specific nanoplatform engaged in malignant lymphoma immunotherapy†
Chen Bai,Pengcheng Hu,Wei Zhang,Lina Song,Di Liu,Yi Chen,Ming Ma,Ning Gu,Yu Zhang
Nanoscale Pub Date : 08/18/2020 00:00:00 , DOI:10.1039/D0NR04450D
Abstract

Nanocarrier systems play an important role in cancer immunotherapy. In this article, biotinylated CD20 and CD3 antibodies were conjugated onto the surface of streptavidin modified ultra-small Fe3O4 nanoparticles via specific binding between streptavidin and biotin to construct a bi-specific nanoplatform (BSNP). The synthesized BSNP with 30 nm hydrodynamic size provides a better magnetic resonance imaging ability than the clinical Gd-chelated contrast agents (r1 value is 5.27 mM−1 s−1 and 4.52 mM−1 s−1 for BSNP and Magnevist, respectively). This nanoplatform can target CD20-positive Raji cells and enhance the T cell mediated cell killing effect in vitro. Further, it can also inhibit tumor growth and prolong the survival time of non-Hodgkin's lymphoma (NHL) xenograft model in vivo. The probable mechanism is that while BSNP can directly induce the apoptosis of Raji cell via aggregation of CD20, T cells are recruited around tumor cells by the BSNP leading to T cell-mediated tumor cell lysis. In addition, the enhanced dual-modal MRI-fluorescence images can be acquired. In summary, the modular designed BSNP provides an efficient immune-related cancer theranostic strategy, which is of great potential as a simple and universal nanoplatform by combining different antibodies to enhance the cancer theranostic efficacy.

Graphical abstract: Modular design of Bi-specific nanoplatform engaged in malignant lymphoma immunotherapy