Polymersomes - can these unique nanoparticles be used to protect the heart?

心梗是冠状动脉疾病患者的急性事件，可导致死亡和损伤。目前，恢复正常血流是主要的治疗方法，但矛盾的是，这种恢复也会导致心肌损伤，即所谓的“致死再灌注损伤”（心肌细胞死亡）。因此，寻找减少致死性再灌注损伤的方法对这些患者至关重要。我们最近发现外泌体——血液中的内源性纳米颗粒——对心脏有保护作用。然而，它们是异质的，难以纯化，因此不是理想的潜在治疗剂。另一方面，聚合体是我们开发的一种完全独特的纳米颗粒，它完全是人工合成的，易于生产，并且可以根据需要进行修改以优化性能。例如，通过修改它们的表面，它们可以被设计成在特定细胞类型表面的目标。我们的两个小组正在合作，首次使用聚合体治疗心脏致命的再灌注损伤。该项目的目的是：1。从荧光标记的聚合体开始，以证明它们的摄取和传递到心脏，特别是到心肌细胞，2。2 .给聚合体装载心脏保护剂，显示它们可以保护心脏免受缺血和再灌注损伤。以各种方式修改聚合体以改善它们，例如，专门针对受伤的心脏（例如：通过LRP1）。主要实验室拥有所有心血管协议：人类肌肉，啮齿动物心脏和其他细胞模型。二级实验室拥有聚合体化学合成所需的一切。我们渴望找到一个热情和有能力的学生愿意把这个项目向前推进。

TA heart attack is the acute event that causes death and injury in patients with coronary artery disease. Currently, restoration of normal blood flow is the main treatment but, paradoxically , this restoration, also causes injury to heart muscle in what is termed "lethal reperfusion injury" (myocardial cell death). Therefore, finding ways to reduce lethal reperfusion injury is vital for these patients.We have recently shown that exosomes - endogenous nanoparticles in the blood - are cardioprotective. However, they are heterogeneous, difficult to purify, and therefore not ideal potential therapeutic agents. Polymersomes, on the other hand, are a totally unique type of nanoparticle we developed that is completely synthetic, can be easily produced, and can be modified as desired to optimize performance. For example, by modifying their surface, they can be designed to home to targets on the surface of specific cell types.Our two groups are collaborating to use polymersomes for the first time to treating lethal reperfusion injury in the heart.The aims of this project are:1. starting with fluorescently labelled polymersomes, to demonstrate their uptake and delivery into the heart, and specifically into cardiac myocytes,2. to load polymersomes with cardioprotective agents and show they can protect the heart against ischaemic and reperfusion injury,3. to modify polymersomes in various ways to improve them, for example targeting them specifically to the injured heart (eg: via LRP1)The primary lab has all cardiovascular protocols in place: human muscle, rodent heart and other cellular models. The secondary lab has everything required for chemical synthesis of polymersomes. We are eager to find an enthusiastic and capable student willing to take this project forward.