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 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 and . Contrast enhancement was monitored US. PDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice ( < 0.05). PDMs + US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments ( < .05). Our results showed that PDMs + US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20+ B cell lymphoma growth . Targeted PDMs could be employed as US molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with US for CD20+ B cell malignancy treatment.