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

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.