Clinically Expired Platelet Concentrates as a Source of Extracellular Vesicles for Targeted Anti-Cancer Drug Delivery

Abstract

The short shelf life of platelet concentrates (PC) of up to 5–7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins. Nevertheless, synthetic drug delivery strategies have significant drawbacks that platelet-derived extracellular vesicles (pEV) can overcome. We investigated, for the first time, the use of pEV as a carrier of the anti-breast cancer drug paclitaxel, considering it as an appealing alternative to improve the therapeutic potential of expired PC. The pEV released during PC storage showed a typical EV size distribution profile (100–300 nm) with a cup-shaped morphology. Paclitaxel-loaded pEV showed significant anti-cancer effects in vitro, as demonstrated by their anti-migratory (>30%), anti-angiogenic (>30%), and anti-invasive (>70%) properties in distinct cells found in the breast tumor microenvironment. We provide evidence for a novel application for expired PC by suggesting that the field of tumor treatment research may be broadened by the use of natural carriers.

Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery

“…Although still limited, these experimental data support the potential for p-EVs for use as TDDSs in various clinical applications [ 8 ]. p-EVs appear to be particularly potent vehicles to deliver their therapeutic payloads specifically to cancer cells [ 262 , 317 ], with the potential to improve retention within the tumor microenvironment (TME), minimize off-target effects, and reduce systemic toxicity [ 8 , 75 , 317 ]. It was speculated that in inflammatory and autoimmune diseases involving a functional role a platelets, p-EVs could be used to deliver immunosuppressive agents or anti-inflammatory drugs to sites of inflammation or autoimmune activity, potentially improving the treatment of conditions like rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis [ 8 , 318 ].…”