Abstract

Background: Cancer is a global health concern with millions of people diagnosed annually. Chemotherapy remains the primary treatment for many cancers despite its toxic side effects. Currently, there is focus on developing nanoparticle systems to enhance the specificity and efficiency of chemotherapeutics. Biological drug delivery methods, e.g., platelets, offer advantages compared to traditional, synthetic nanoparticles and may enhance therapeutic potency by avoiding immune interactions. Platelets are a potential source of biological nanoparticles for drug delivery but, their short shelf-life limits their therapeutic potential. Lyophilization has been used to increase the shelf-life and stability of platelets. Methods: Here, we evaluate a modified version of Cellphire’s proprietary freezedried platelet product loaded with the cytotoxic drug, doxorubicin, for delivery to hemangiosarcoma cells. Results: We demonstrate that 1-10% volume/volume (v/v) addition of doxorubicin-loaded Lyophilized Human Platelets (DOX-LHP) to hemangiosarcoma cultures have potent anticancer activity by inhibiting proliferation, metabolism, and promoting apoptosis. Further, hemangiosarcoma cells exposed to 5% and 10% v/v DOX-LHP contained 2.2x and 4x more intracellular doxorubicin compared to cells treated with media containing 5 µM free doxorubicin. Conclusions: These results suggest that lyophilized, DOX-LHP overcome the storage limitations of platelets and once reconstituted they function as effective drug delivery vehicles for cytotoxic compounds.

Keywords

drug delivery, platelets, cancer cell targeting, biological nanoparticles, lyophilization