Overcoming the blood–brain barrier by using a multistage exosome delivery system to inhibit central nervous system lymphoma

Due to the presence of blood-brain barrier (BBB), various chemotherapy drugs against B-cell lymphoma cannot be effectively transmitted into the brain, leading to poor prognosis of primary central nervous system lymphoma (PCNSL). Exosomes can cross the BBB as a bio- and immune-compatible drug carrier. In this study, we developed a novel drug delivery system, in which the exosomes (Exo) are conjugated with anti-CD22 monoclonal antibody fragments (CD22-F(ab')2) and encapsulate doxorubicin (DOX) to form CD22-F(ab')2-Exo-DOX. We showed that CD22-F(ab')2-Exo-DOX can cross BBB and deliver DOX precisely to tumor cells. The average apoptosis rate of lymphoma cells was 84.60% ± 10.69%. The tumor-bearing mice treated with CD22-F(ab')2-Exo-DOX have significantly prolonged life expectancy and the enhanced anti-tumor activity. CD22-F(ab')2-Exo-DOX might be ingested by brain microvascular endothelial cells through endocytosis to cross the BBB. Therefore, targeted chemotherapy mediated by CD22-F(ab')2-Exo-DOX is a promising option for the treatment of PCNSL.