Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis

Abstract

Background: Despite tremendous advancement, cancer still remains one of the leading causes of death worldwide. Inefficiency of current drug delivery regimens is one important factor that limits the therapeutic efficacy of existing drugs, thus contributing to cancer mortality. To address this limitation, synthetic nanotechnology-based delivery systems have been developed; however, they raise concern of inducing adverse immunogenic reactions. Exosomes (Exos) are nonimmunogenic nano-sized vesicles that have received significant attention as efficient drug delivery system. Methods: Drug loading in Exos were achieved by incubating different cell types viz pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs), and macrophages (MØs) with Doxorubicin (DOX). Differential ultracentrifugation was performed to isolate exosome and their size was determined by dynamic light scattering analysis. The efficacy of drug packaging into Exos was evaluated by HPLC. Flow cytometry was performed to examine the apoptosis. Cell viability was determined using the WST-1 assay. Results: PCCs shed the most Exos and were the most efficient in drug loading followed by MØs and PSCs as examined by HPLC quantification. However, when compared for antitumor efficacy, MØ-derived Exos loaded with DOX (MØ-Exo-DOX) showed highest activity followed by PSCs and PCCs. Conclusion: These varying antitumor activities likely resulted from nondrug contents of Exos since we did not observe any significant differences in their uptake by the cancer cells. Altogether, our data suggest that donor cell-specific differences exist in Exos, which could influence their utility as drug carrier for therapeutic purposes.