Department of Pharmaceutics, Harbin Medical University, Heilongjiang, 163319, People's Republic of China.
Department of Physiology, Harbin Medical University, Heilongjiang, 163319, People's Republic of China.
Int J Nanomedicine. 2024 Nov 6;19:11275-11292. doi: 10.2147/IJN.S478276. eCollection 2024.
Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.
In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.
We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.
Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.
心肌缺血再灌注（IR）损伤与心脏微血管损伤密切相关。据报道，大蒜素（AL）能有效保护心脏微血管系统免受 IR 损伤。然而，目前药物的治疗效果不尽如人意，且药物向受损心脏的输送不足仍然是主要关注点。受中性粒细胞与炎症状态下的心脏微血管内皮细胞（CMEC）之间天然相互作用的启发，构建了一种基于中性粒细胞膜伪装的纳米颗粒，旨在通过改善药物向受损心脏的递送，实现对 IR 损伤的非侵入性主动靶向治疗。
在这项研究中，我们构建了一种载有 AL 的介孔硅纳米颗粒（MSNs）包裹的中性粒细胞膜作为药物递送系统。通过小动物活体成像系统评估了纳米颗粒（命名为 AL@MSNs@NM）对梗死心肌的特异性靶向能力。通过动物超声成像系统、HE 染色和激光散斑成像系统评估了 AL@MSNs@NM 处理后的心脏功能。通过 ELISA 试剂盒、免疫荧光和 PCR 分析了治疗机制。
我们发现，AL@MSNs@NM 显著改善了心脏功能指标，减少了梗死面积和纤维化，增加了缺血区的血管灌注，同时促进了 CMEC 的功能，包括迁移、管腔形成、切应力适应和一氧化氮产生。进一步的研究表明，AL@MSNs@NM 通过抑制 CMEC 铁死亡和增加血小板内皮细胞黏附分子-1（PECAM-1）的表达，发挥对 IR 大鼠的心脏保护作用。
我们的结果表明，AL@MSNs@NM 可显著逆转 CMEC 的铁死亡，增加 PECAM-1 的表达，增强心脏功能，减少心肌梗死面积。因此，这项策略表明，工程仿生纳米技术可有效递送 AL 进行心肌梗死的靶向治疗。
