Recent advances in platelet engineering for anti-cancer therapies

Platelets contribute a major role in hemostasis by clumping and coagulation at the site of blood vessel injuries. In light of recent findings of a close relationship between platelets and immunological response, as well as interactions between platelets and cancer cells, novel engineering strategies have emerged for the integration of platelets or platelet membrane (PM) with anti-cancer therapeutics. In this review, we discuss several recent innovations that use platelets or their membranes to circumvent host immune responses and target tumor cells with high specificity to deliver a range of pharmacological, photothermal, or immunologic agents for eradication of recalcitrant tumor cells. More specifically, we compare the relative advantages of using whole platelets versus single or hybrid PM to coat nanoparticle cargoes. These cargoes range from well-established anti-tumor apoptosis-inducing agents, to relatively new photothermal agents that can induce a feedback cascade in which they induce vascular damage to the tumor which recruits more platelet- or membrane-encapsulated agents to induce further damage. We also discuss the use of engineered platelets to produce programmed cell death-inducing platelet derived microparticles. This review provides an overview and future directions for this promising platelet-based biomimetic approach to anti-cancer therapy.

血小板通过在血管损伤部位聚集和凝固，在止血过程中发挥重要作用。鉴于近期发现血小板与免疫反应之间存在密切关联，以及血小板与癌细胞之间的相互作用，将血小板或血小板膜（PM）与抗癌疗法相结合的新型工程策略应运而生。本综述探讨了近期多项创新成果，这些成果利用血小板或其膜来规避宿主免疫反应，并以高特异性靶向肿瘤细胞，递送多种药理学、光热学或免疫学制剂，以根除难治性肿瘤细胞。更具体地说，我们比较了使用完整血小板与单一或混合PM包覆纳米颗粒载体的相对优势。这些载体涵盖了成熟的抗肿瘤凋亡诱导剂，以及相对较新的光热剂——这类光热剂可触发反馈级联反应：它们诱导肿瘤血管损伤，进而招募更多血小板或膜包裹的制剂，以造成进一步损伤。我们还探讨了利用工程化血小板生成诱导程序性细胞死亡的血小板衍生微粒的方法。本综述概述了这一极具前景的基于血小板的仿生抗癌治疗方法，并展望了其未来发展方向。