Synergic fabrication of pembrolizumab loaded doxorubicin incorporating microbubbles delivery for ultrasound contrast agents mediated anti-proliferation and apoptosis

This study evaluated pembrolizumab-conjugated, doxorubicin (DOX)-loaded microbubbles (PDMs) in combination with ultrasound (US) as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Pembrolizumab, a monoclonal CD20 antibody, was attached to the surfaces of DOX-loaded microbubbles. PDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of PDMs in combination with ultrasound (PDMs + US) were evaluated in vitro in CD20+ and CD20- cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20-) lymphoma cell-grafted mice. PDMs specifically bound to CD20+ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via US. PDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (p