Department of Pharmacology, Columbia University, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):82-6. doi: 10.1073/pnas.1220038110. Epub 2012 Dec 17.
The pH (low) insertion peptide (pHLIP) family enables targeting of cells in tissues with low extracellular pH. Here, we show that ischemic myocardium is targeted, potentially opening a new route to diagnosis and therapy. The experiments were performed using two murine ischemia models: regional ischemia induced by coronary artery occlusion and global low-flow ischemia in isolated hearts. In both models, pH-sensitive pHLIPs [wild type (WT) and Var7] or WT-pHLIP-coated liposomes bind ischemic but not normal regions of myocardium, whereas pH-insensitive, kVar7, and liposomes coated with PEG showed no preference. pHLIP did not influence either the mechanical or the electrical activity of ischemic myocardium. In contrast to other known targeting strategies, the pHLIP-based binding does not require severe myocardial damage. Thus, pHLIP could be used for delivery of pharmaceutical agents or imaging probes to the myocardial regions undergoing brief restrictions of blood supply that do not induce irreversible changes in myocytes.
pH（低）插入肽（pHLIP）家族能够靶向细胞外 pH 值较低的组织。在这里，我们表明，缺血性心肌是靶向的，这可能为诊断和治疗开辟了新途径。实验使用两种小鼠缺血模型进行：冠状动脉阻塞引起的局部缺血和分离心脏中的全局低流量缺血。在这两种模型中，pH 敏感的 pHLIP（野生型（WT）和 Var7）或 WT-pHLIP 包被的脂质体与缺血但不是正常的心肌区域结合，而 pH 不敏感的 kVar7 和包被有 PEG 的脂质体则没有偏好。pHLIP 不影响缺血心肌的机械或电活动。与其他已知的靶向策略不同，基于 pHLIP 的结合不需要严重的心肌损伤。因此，pHLIP 可用于将药物制剂或成像探针递送至经历短暂血液供应限制但不引起肌细胞不可逆变化的心肌区域。
