Engineering platelets as cancer therapeutics

Accumulating evidence indicates that platelets promote cancer progression through direct interactions with malignant cells, the secretion of soluble mediators and the release of platelet-derived extracellular vesicles. In certain contexts, platelets can also suppress tumour progression by modulating immune responses, delivering antiproliferative microRNAs or releasing inhibitory factors. This dynamic and context-dependent interplay limits the effectiveness of strategies that solely inhibit or activate platelet activity and has driven the development of engineering approaches to reprogramme platelets with therapeutic intent. Unlike most cellular products, platelet-based approaches can be implemented in both autologous and allogeneic settings, providing more flexible approaches for developing new therapies. Over the past few years, advances in genetic and chemical engineering have enabled the multifunctional modification of platelets while preserving native properties essential for cancer therapy. Engineered platelets can act as targeted delivery vehicles to enhance local drug accumulation and release, or as active effector cells that directly modulate tumour progression. The clinical implementation of these engineered products will require control of platelet stability and activation, scalable manufacturing processes and rigorous safety evaluation. In this Review, we summarize the current understanding of platelet biology in cancer, examine engineering strategies for their therapeutic use, and outline opportunities and challenges for their clinical translation.