IntroductionCancer-related drug expenses are rising with the increasing cancer incidence and cost may represent a severe challenge for drug access for patients with cancer. Consequently, strategies for increasing therapeutic efficacy of already available drugs may be essential for the future health-care system.Areas coveredIn this review, we have investigated the potential for the use of platelets as drug-delivery systems. We searched PubMed and Google Scholar to identify relevant papers written in English and published up to January 2023. Papers were included at the authors' discretion to reflect an overview of state of the art.Expert opinionIt is known that cancer cells interact with platelets to gain functional advantages including immune evasion and metastasis development. This platelet-cancer interaction has been the inspiration for numerous platelet-based drug delivery systems using either drug-loaded or drug-bound platelets, or platelet membrane-containing hybrid vesicles combining platelet membranes with synthetic nanocarriers. Compared to treatment with free drug or synthetic drug vectors, these strategies may improve pharmacokinetics and selective cancer cell targeting. There are multiple studies showing improved therapeutic efficacy using animal models, however, no platelet-based drug delivery systems have been tested in humans, meaning the clinical relevance of this technology remains uncertain.

Platelets can modulate cancer through budding of platelet microparticles (PMPs) that can transfer a plethora of bioactive molecules to cancer cells upon internalization. In acute myelogenous leukemia (AML) this can induce chemoresistance, partially through a decrease in cell activity. Here we investigated if the internalization of PMPs protected the monocytic AML cell line, THP-1, from apoptosis by decreasing the initial cellular damage inflicted by treatment with daunorubicin, or via direct modulation of the apoptotic response. We examined whether PMPs could protect against apoptosis after treatment with a selection of inducers, primarily associated with either the intrinsic or the extrinsic apoptotic pathway, and protection was restricted to the agents targeting intrinsic apoptosis. Furthermore, levels of daunorubicin-induced DNA damage, assessed by measuring gH2AX, were reduced in both 2N and 4N cells after PMP co-incubation. Measuring different BCL2-family proteins before and after treatment with daunorubicin revealed that PMPs downregulated the pro-apoptotic PUMA protein. Thus, our findings indicated that PMPs may protect AML cells against apoptosis by reducing DNA damage both dependent and independent of cell cycle phase, and via direct modulation of the intrinsic apoptotic pathway by downregulating PUMA. These findings further support the clinical relevance of platelets and PMPs in AML.

The role of platelets in cancer development and progression is increasingly evident, and several platelet–cancer interactions have been discovered, including the uptake of platelet microparticles (PMPs) by cancer cells. PMPs inherit a myriad of proteins and small RNAs from the parental platelets, which in turn can be transferred to cancer cells following internalization. However, the exact effect this may have in acute myelogenous leukemia (AML) is unknown. In this study, we sought to investigate whether PMPs could transfer their contents to the THP-1 cell line and if this could change the biological behavior of the recipient cells. Using acridine orange stained PMPs, we demonstrated that PMPs were internalized by THP-1 cells, which resulted in increased levels of miR-125a, miR-125b, and miR-199. In addition, co-incubation with PMPs protected THP-1 and primary AML cells against daunorubicin-induced cell death. We also showed that PMPs impaired cell growth, partially inhibited cell cycle progression, decreased mitochondrial membrane potential, and induced differentiation toward macrophages in THP-1 cells. Our results suggest that this altering of cell phenotype, in combination with decrease in cell activity may offer resistance to daunorubicin-induced apoptosis, as serum starvation also yielded a lower frequency of dead and apoptotic cells when treated with daunorubicin.

The Blood Far Forward (BFF) research program was established to conduct blood product efficacy and safety studies, donor performance studies, and research on optimal training methods to improve the safety of blood collection and transfusion performed by Norwegian Naval Special Operation Commando soldiers. The use of intravenous fluids for volume replacement during hemorrhagic shock is controversial, but it is currently the standard of care. In the far‐forward environment, large volume resuscitation for massive bleeding is a great challenge. Crystalloid and colloid solutions add weight and bulk to the medic's kit, require temperature sensitive storage, and should be warmed before infusion to prevent hypothermia. Excessive use of these solutions causes a dilutional coagulopathy, acidosis, and potentially increased inflammatory injury compared with blood products. Type‐specific whole blood from an uninjured combat companion on the other hand is almost always available. It is warm, replaces intravascular volume, and provides oxygen delivery and hemostatic capacity to prevent or treat shock and coagulopathy. Whole blood may be ideal for the resuscitation of combat casualties with hemorrhagic shock. BFF program pilot studies on use of platelet‐sparing leukoreduction filters, whole blood transport tolerance, donor performance, and autologous reinfusion of 24‐hour ambient temperature stored whole blood have been performed and suggest the feasibility of expanding whole blood use in resuscitation. If successful, the BFF program will change tactics, techniques, and procedures with a new lifesaving capability.