Department of Surgery, University of North Carolina, Chapel Hill, NC, 27599, USA.
Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.
Biomaterials. 2021 Jul;274:120862. doi: 10.1016/j.biomaterials.2021.120862. Epub 2021 Apr 29.
Smoke inhalation injury is associated with significant mortality and current therapies remain supportive. The purpose of our study was to identify proteins upregulated in the lung after smoke inhalation injury and develop peptide amphiphile nanofibers that target these proteins. We hypothesize that nanofibers targeted to angiotensin-converting enzyme or receptor for advanced glycation end products will localize to smoke-injured lungs.
Five targeting sequences were incorporated into peptide amphiphile monomers methodically to optimize nanofiber formation. Nanofiber formation was assessed by conventional transmission electron microscopy. Rats received 8 min of wood smoke. Levels of angiotensin-converting enzyme and receptor for advanced glycation end products were evaluated by immunofluorescence. Rats received the targeted nanofiber 23 h after injury via tail vein injection. Nanofiber localization was determined by fluorescence quantification.
Peptide amphiphile purity (>95%) and nanofiber formation were confirmed. Target proteins were increased in smoke inhalation versus sham (p < 0.001). After smoke inhalation and injection of targeted nanofibers, we found a 10-fold increase in angiotensin-converting enzyme-targeted nanofiber localization to lung (p < 0.001) versus sham with minimal localization of non-targeted nanofiber (p < 0.001).
We synthesized, characterized, and evaluated systemically delivered targeted nanofibers that localized to the site of smoke inhalation injury in vivo. Angiotensin-converting enzyme-targeted nanofibers serve as the foundation for developing a novel nanotherapeutic that treats smoke inhalation lung injury.
吸入性烟雾损伤与高死亡率相关，目前的治疗方法仍以支持治疗为主。本研究旨在鉴定吸入性烟雾损伤后肺组织中上调的蛋白，并制备靶向这些蛋白的肽两亲性纳米纤维。我们假设靶向血管紧张素转换酶（ACE）或晚期糖基化终产物受体（RAGE）的纳米纤维将定位于烟雾损伤的肺组织。
采用逐步掺入的方法将 5 种靶向序列整合到肽两亲性单体中，以优化纳米纤维的形成。采用常规透射电子显微镜评估纳米纤维的形成。大鼠吸入 8 min 木质烟雾。采用免疫荧光法评估 ACE 和 RAGE 水平。损伤后 23 h 经尾静脉注射给予靶向纳米纤维。通过荧光定量确定纳米纤维的定位。
肽两亲性单体的纯度（>95%）和纳米纤维的形成得到了确认。与假手术组相比，烟雾吸入组的 ACE 和 RAGE 均增加（p < 0.001）。烟雾吸入和靶向纳米纤维注射后，我们发现 ACE 靶向纳米纤维在肺组织中的定位增加了 10 倍（p < 0.001），而与假手术组相比，非靶向纳米纤维的定位明显减少（p < 0.001）。
我们合成、表征并评估了系统给予的靶向纳米纤维，其在体内定位于烟雾吸入损伤部位。ACE 靶向纳米纤维为开发治疗烟雾吸入性肺损伤的新型纳米治疗方法奠定了基础。
