Vascular Repair by Grafting Based on Magnetic Nanoparticles: Comparison
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磁性纳米粒子（MNPs）由于其独特的磁响应性在过去几十年中引起了广泛关注。尤其是在疾病的诊断和治疗方面，大多采用无创方式，取得了较好的效果。MNPs的磁响应受到合成颗粒的尺寸、结晶度、均匀性和表面性质的严格控制。在这篇综述中，我们总结了 MNP 的分类及其在血管修复中的应用。MNPs主要利用其独特的磁特性参与血管修复，包括磁刺激、磁驱动、磁共振成像、磁热疗、磁组装支架、磁靶向给药等，可显着影响支架性能、细胞行为、因子分泌、药物释放等。以有创方式参与血管修复并建立连续检测过程仍是未来的发展方向。agnetic nanoparticles (MNPs) have attracted much attention in the past few decades because of their unique magnetic responsiveness. Especially in the diagnosis and treatment of diseases, they are mostly involved in non-invasive ways and have achieved good results. The magnetic responsiveness of MNPs is strictly controlled by the size, crystallinity, uniformity, and surface properties of the synthesized particles. 

  • magnetic nanoparticles
  • vascular repair
  • magnetic responsiveness

1. 血管移植物中的Magnetic nanoparticles (MNPs) in Vascular Grafts

血管移植物（也称为血管支架）一直是临床有效的治疗血管疾病或暴力侵袭引起的大血管缺损的策略[Vascular grafts (also called vascular scaffolds) have always been a clinically effective treatment strategy for large vascular defects caused by vascular disease or violent invasion [1][2][3], such as polyurethane (PU) [4], polyester 4,79,80]，如聚氨酯（PU）[81 ]、聚酯（PET）[(PET) 82[5], ]、ePTFE [6], [etc. Although these vascular grafts, when used 83in ]larger-diameter 等。虽然这些血管移植物在用于大直径血管vessels (>6 mm) 时显示出令人满意的长期性能，但它们在小直径血管 show satisfactory long-term performance, they display inferior performance in small-diameter vessels (<6 mm) 中表现出较差的性能，主要是因为它们容易发生内膜增生, mainly because they are prone to intimal hyperplasia (IH) 和血栓形成and thrombogenesis [7]. Given the above-mentioned unsatisfactory factors and the shortcomings of secondary operations caused by non-degradability, it has always been a goal to seek natural materials with better biocompatibility to construct vascular grafts. Unfortunately, the many properties of natural materials cannot meet the [application 84]。鉴于上述不理想的因素以及不可降解性导致二次手术的缺点，寻求生物相容性更好的天然材料来构建血管移植物一直是一个目标。不幸的是，天然材料的许多特性不能满足血管移植物的应用要求，例如机械强度requirements [of 85vascular ]、弹性grafts, [such 16as ]mechanical 和降解strength [[8], 86elasticity [9], 87and degradation [10][11]. ]。MNPs 被认为可以有效提高血管移植物的性能，并在其他领域提供更多应用（例如 MRIare believed to effectively improve the performance of vascular grafts and provide more applications in other areas (such as MRI [12] or [nano-modification 43[13]). ]Ghorbani 或纳米修饰 [et al. 88[14] ]）。戈尔巴尼等人。[synthesized 89]通过共沉淀技术合成了INOPs，它们均匀分布在 by co-precipitation technique and they were evenly distributed in PLGA-明胶支架中。结果表明，添加的MNPs对孔形貌无特殊影响，但略微降低了孔径分布。含有该结构的MNPs具有增强的机械强度，但吸收能力和生物降解率降低。我们之前的研究gelatin scaffolds. The results showed that the added MNPs had no special effect on the pore morphology but slightly reduced the pore size distribution. The MNPs containing the construct had enhanced mechanical strength, but the absorption capacity and biodegradation rate were reduced. Our previous study [[9] 16also ]proved 也证明了that MNPs 通过浸润均匀分布在丝素蛋白支架中。结果表明，所获得的磁性丝素蛋白支架显着延缓了降解速率，增强了机械强度。莱卡库等人。[were evenly distributed in silk fibroin scaffolds by infiltration. The results showed that the obtained magnetic silk fibroin scaffolds significantly delayed the degradation rate and enhanced mechanical strength. Lekakou et al. [15] found 90]that 发现明胶gelatin/弹性蛋白凝胶是纳米复合支架，其扁平的弹性蛋白纳米域嵌入明胶基质中，模拟动脉介质的结构。他们研究了明胶/“羟基磷灰石”（HA）纳米复合材料支架，并在溶液中原位生成了“HA”。当施加9.4 T的磁场时，明胶中的HA颗粒和明胶微纤维的取向垂直于磁场方向，为制备动脉血管层状支架提供了基础。默滕斯等人。[elastin gels are nanocomposite scaffolds with flattened elastin nanodomains embedded in a gelatin matrix that mimic the structure of the arterial media. They studied gelatin/“hydroxyapatite” (HA) nanocomposite scaffolds, and “HA” was generated in situ in solution. When a magnetic field of 9.4 T was applied, the HA particles and gelatin microfibrils in the gelatin were oriented perpendicular to the direction of the magnetic field, which provided a basis for the preparation of arterial vascular layered scaffolds. Mertens et al. [16] prepared three ultra-small superparamagnetic iron oxide 20]nanoparticles 制备了三个超小的超顺磁性氧化铁纳米粒子（(USPIO），随后通过化学交联将其直接定植在胶原支架中，并间接用作成像移植支架。在无细胞植入物的情况下也可以进行成像，以可视化胶原支架在体内的降解，这有利于分析体内降解周期和快速降解天然材料的机制。目前，添加MNP的血管移植物主要用于提高机械强度，主要是基于高模量、丰富的官能团。和 MNP), which were subsequently directly colonized in collagen scaffolds by chemical cross-linking and used indirectly as imaging graft scaffolds. Imaging can also be performed in the case of acellular implants to visualize the degradation of collagen scaffolds in vivo, which is beneficial for analyzing the in vivo degradation cycle and mechanism of rapidly degrading natural materials. Currently, MNP-added vascular grafts are mainly used to improve mechanical strength, mainly based on the high modulus, abundant functional groups. and uniform dispersion of MNPs 的均匀分散 [ 91 ]。[17].

2. MNPs 调节血管相关细胞行为和因子表达Regulate Vascular-Related Cell Behavior and Factor Expression

血管损伤修复是一项高度组织化的工程，主要涉及炎症、新内膜和重塑三个阶段[ Vascular injury repair is a highly organized engineering that mainly involves three stages, including inflammation, neointima, and remodeling [18]. For the initial acute inflammation stage, many macrophages will migrate to the injury site and secrete various inflammatory factors (such 10as ]。对于初期的急性炎症阶段，许多巨噬细胞会迁移到损伤部位，分泌各种炎症因子（如TNF-α、IL-6、MCP-1），清除受损细胞碎片，起到防御作用。当进入炎症晚期并过渡到新内膜阶段（活性再内皮化阶段）时，巨噬细胞分泌各种修复细胞因子（如bFGF、VEGF、TGF-β）来调节损伤部位的微环境。因此，它调节参与再内皮化的各种细胞的行为，包括粘附、迁移、增殖、表型和归巢, IL-6, MCP-1) to clear the damaged cell debris and play a defensive role. When entering the late stage of inflammation and transitioning to the neointimal stage (active re-endothelialization stage), macrophages secrete various repair cytokines (such as bFGF, VEGF, and TGF-β) to regulate the microenvironment at the injury site. Thus, it regulates the behavior of various cells involved in re-endothelialization, including adhesion, migration, proliferation, phenotype, and homing [19][20]. However, regardless of the stage, various related cells and [factors 92are involved, and favorable cell 93]。然而，无论处于哪个阶段，都涉及各种相关的细胞和因子，有利的细胞行为和因子分泌可以迅速重塑血管。大量研究证明，behavior and factor secretion can rapidly remodel blood vessels. Numerous studies have proved that the unique magnetic properties of MNPs 独特的磁性可以调节细胞行为和因子分泌，从而促进血管重塑[can regulate cell behavior and factor secretion, thereby promoting vascular remodeling 94[21]. ]。MNPs 通过以下方式调节细胞行为和因子分泌： regulate cell behavior and factor secretion in the following ways: (1) MNPs 通过刺激标记细胞； through the stimulation of labeled cells; (2) MNPs 标记的细胞对磁场有反应；-labeled cells respond to magnetic fields; (3) MNPs与材料结合，影响贴壁细胞行为和因素； bind to materials to affect adherent cell behavior and factors; (4) MNPs通过影响相关通路间接影响靶细胞的行为和因子分泌。Lshii 等人。[ indirectly affect the behavior and factor secretion of target cells by affecting related pathway. Lshii et al. [22] assembled a magnetic cell sheet by combining 95 ] 通过结合 Fe Fe3 O组装磁性细胞片4纳米颗粒与间充质干细胞 nanoparticles with mesenchymal stem cells (MSCs)，然后将它们移植到裸鼠的后肢，以评估血管生成的潜力。结果表明，磁性细胞片组血管生成更多，血管内皮生长因子表达增加，细胞凋亡减少。佩雷亚等人。[ and then transplanted them into the hind limbs of nude mice to evaluate the potential of angiogenesis. The results showed that the magnetic cell sheet group had more angiogenesis, increased vascular endothelial growth factor expression, and decreased 96]apoptosis. 首先用MNPerea et al. [23] firs标记人平滑肌细胞（t labeled human smooth muscle cells (SMCs）和人脐静脉内皮细胞（) and human umbilical vein endothelial cells (HUVECs），然后利用径向磁力驱动细胞有效到达管状支架的管腔表面，将细胞固定在基质表面，粘附牢固，有效促进了血管内皮化进程。为了克服血管修复手术对内皮细胞层造成的不可逆损伤，导致血管功能受损和再狭窄，) with MNPs and then used radial magnetic force to drive the cells to efficiently reach the lumen surface of tubular scaffolds, fixed the cells on the matrix surface, and adhered firmly, which effectively promoted the process of vascular endothelialization. To overcome irreversible damage to the endothelial cell layer caused by surgery in repairing blood vessels, resulting in impaired vascular function and restenosis, Vosen 和他的团队and his team [21] combined nanotechnology with gene and cell therapy for site-specific re-endothelialization and restoration of vascular function. The researchers overexpressed the vascular protection gene endothelial [nitric 94]oxide 将纳米技术与基因和细胞疗法相结合，用于位点特异性再内皮化和血管功能的恢复。研究人员使用慢病毒载体和synthase MNP 的复合物在内皮细胞 (EC) 中过度表达血管保护基因内皮一氧化氮合酶 (eNOS)。负载 MNPs 和过表达 eNOS 的细胞具有磁性，即使在流动条件下，它们也可以通过磁场以径向对称的方式定位在血管壁上。结果表明，处理后的血管显示出增强的 eNOS 表达和活性。此外，在血管损伤小鼠模型中，用过表达 eNOS 的细胞替代 EC 可恢复内皮功能。更有趣的是，(eNOS) in endothelial cells (ECs) using a complex of lentiviral vectors and MNPs. MNPs-loaded and eNOS-overexpressing cells are magnetic, and even under flow conditions, they can be positioned on the vessel wall in a radially symmetric manner by the magnetic field. The results demonstrated that the treated vessels showed enhanced eNOS expression and activity. Furthermore, the replacement of ECs with eNOS-overexpressing cells restored endothelial function in a mouse model of vascular injury. More interestingly, Mattix et al. [24] added MNPs 等人。[to the cell spheres 97]through 通过the Janus 方法将 MNPs 添加到细胞球中，然后通过外部磁场method and then manipulated the cell sphere to fuse into a vascular tissue structure with a diameter of 5 mm through the magnetic force generated by the external magnetic field (EMF) 产生的磁力操纵细胞球融合成直径为 5 mm 的血管组织结构。对于 MNP 与材料的结合，. For the binding of MNPs to materials, Filippi 等人。[et al. [25] prepared novel magnetic nanocomposite hydrogels 98]by 通过将incorporating MNP 掺入含有来自人类脂肪组织基质血管部分s into PEG-based hydrogels containing cells from the stromal vascular fraction (SVF) 的细胞的基于 PEG 的水凝胶中，制备了新型磁性纳米复合水凝胶；研究了外部静磁场 of human adipose tissue; the stimulation of an external static magnetic field (SMF) 对构建体的血管生成特性的刺激。结果显示内皮细胞、周细胞和血管周围基因被强烈激活，VEGF和 on the angiogenic properties of the constructs were investigated. The results showed that endothelial cells, pericytes, and perivascular genes were strongly activated, and the expressions of VEGF and CD31(+)的表达增加。在小鼠皮下移植后，磁驱动结构显示出更致密、更矿化和更快血管化的组织。顾等人。[ were increased. After subcutaneous transplantation in mice, the magnetic drive structure showed denser, more mineralized, and faster-vascularized tissue. Gu et al. [26] studied iron oxide nanoparticles 99]to 研究了氧化铁纳米颗粒通过影响干扰素调节因子regulate 5 (IRF5) 信号通路来调节巨噬细胞表型向 M1 极化和下调 M2 相关精氨酸酶macrophage phenotype toward M1 polarization and down-regulate M2-related arginase 1 (Arg-1)，其中铁基 MNP 具有抗癌和抗癌作用。抑制肿瘤血管生成，提供新的见解。然而，MNPs 对巨噬细胞的表型极化具有浓度依赖性影响。许多研究表明，低剂量的 MNPs 也可以促进 M2 极化，但相关途径机制研究很少[ by affecting the interferon regulatory factor 5 (IRF5) signaling pathway, in which iron-based MNPs are anti-cancer and inhibit tumor angiogenesis, providing new insights. However, MNPs have a concentration-dependent effect on the phenotypic polarization of macrophages. Many studies have shown that low-dose MNPs also can promote M2 polarization, but the related pathway mechanism is rarely studied [27][28]. The aforementioned favorable behaviors based on cell and 100factor ,secretion 101regulation ]。上述基于by MNPs 调节细胞和因子分泌的有利行为可以有效地参与血管修复。can effectively participate in vascular repair.

3. MNPs as Carriers 作为靶向给药的载体for Targeted Drug Delivery

MNPs have unique advantages in the construction of drug delivery systems (magnetic drug delivery, MDD), such as inherent magnetic targeting, magnetocaloric drug release, and accessible surface modification, which can maximize drug delivery. By applying a permanent magnet near the target tissue, the accumulation of MNPs at the target site can be induced, reducing the drug’s distribution in the whole body, thereby improving the therapeutic effect and reducing the toxic and side effects [104][29]. When using MNPs as drug delivery systems, the magnetic properties of nanoparticles are size-dependent, and magnetic nanoparticles with excellent performance can be obtained by adjusting the size. The charge and hydrophobic properties of MNPs affect their interactions with plasma proteins, the immune system, extracellular matrix, or non-targeted cells and determine their biological distribution. Hydrophobic MNPs readily adsorb plasma proteins, leading to recognition by the reticuloendothelial system and eventual clearance from the circulatory system under opsonization, resulting in a short circulating half-life. After modifying its surface with hydrophilic PEG and other molecules, its circulating half-life can be increased. Positively charged MNPs easily bind to non-targeted cells and undergo a nonspecific internalization process. Compared with negatively charged MNPs, positively charged MNPs generally exhibit higher cellular internalization effects [105,106][30][31]. In recent years, MDD systems have been widely developed to treat various diseases [107[32][33],108], including tumors, such as designing Fe3O4 nanoparticles-based targeted drug delivery systems to enhance cancer targeting to suppress tumors under static magnetic fields and laser irradiation growth, and the system proved effective for in situ transdermal drug delivery, magnetic fields, and synchronization of laser and biological targeting. Demonstrated in breast cancer models, this system is an effective alternative for the treatment of superficial cancers [109][34]; bone, for example, has developed an exosome derived from neutrophils modified by sub-5 nm ultra-small PBNP (uPB) engineering through click chemistry, which can target deep into cartilage, significantly improve the joint injury of CIA mice, and inhibit the overall severity of arthritis, showing considerable potential in the clinical diagnosis and treatment of arthritis [110][35]; in vascular structures, a developed nanoparticle (MMB-PLGA-PTX) can be used for in-stent restenosis (ISR) treatment that is responsive to external magnetic fields and LIFU. The results showed that magnetic targeting increased the accumulation of MMP-PLGA-PTX 10-fold, while LIFU facilitated the penetration of the released PLGA-PTX into the arterial tissue, thereby increasing the retention time of the released PTX in the stented vascular tissue. Combined with efficacy, this strategy holds great promise for the precise delivery of antiproliferative drugs to stented vascular tissue for ISR therapy [111][36]; skin, such as heme-modified prussian blue nanoparticles (PBNP, an iron-based magnetic nanoparticle) forms a colloid with NO, which is locally dropped at the skin wound site in response to NIR light and releases NO in a targeted and controllable manner to enhance blood Microcirculation, thereby effectively enhancing angiogenesis and collagen deposition during skin wound healing [112][37] . In the treatment of vascular injury, the main focus is on treating the etiology [113][38]. For example, arterial occlusion caused by external force injury or cardiovascular disease can cause severe mortality [114[39][40],115], so the rapid recanalization strategy can effectively reduce the risk of death. Intravenous injection of tissue plasminogen activator (tPA) at a fixed dose is the main method to dredge arterial occlusion [116,117][41][42]. Still, it will produce complications such as insufficient curative effect and bleeding. Therefore, magnetic drug targeting (MDT) is an effective therapeutic method, which uses an EMF to enhance the specific accumulation of drugs bound to MNPs in the diseased vascular system [118][43]. Ma et al. [119][44] first studied the possibility of local thrombolysis with MDT. MNPs combined with tPA (tPA equivalent is 0.2 mg/kg) were used in the rat embolism model. In this study, MNPs administered intravascularly moved and accumulated along the iliac artery affected by thrombus under the action of an external magnet, which resulted in effective targeted thrombolysis and was only less than 20% of the free tPA dose. Atherosclerosis (AS) is also a severe disease that can cause vascular damage [120,121][45][46]. Although many drugs can treat atherosclerosis [122[47][48][49],123,124], their systemic administration has serious disadvantages. In particular, the proportion of therapeutic dose reaching atherosclerotic lesions is small, resulting in poor therapeutic effect. Increasing the dose is often impossible in many cases because it can cause serious side effects and drug tolerance. Since the existing treatment strategies for AS are far from ideal, there is an urgent need for targeted therapy as an alternative strategy to exert better therapeutic effects. Cicha et al. [125][50] developed the combination of dexamethasone on MNPs, which magnetically targeted the balloon injury area in rabbits as well as advanced atherosclerotic plaques. Although the desired effect was not achieved, this may also be due to the selection of candidate drugs. In addition, myocardial infarction caused by coronary plaque rupture can also cause severe inflammation and even heart failure [126,127,128][51][52][53]. Zhang et al. [129][54] studied in a rat myocardial infarction model, using an in vitro epicardial magnet to accumulate MNPs that bind to the human VEGF gene encoded by an adenovirus vector in the ischemic area. Results showed that targeting MNPs resulted in higher VEGF gene expression in the affected area and better cardiac repair. Currently, the treatment of myocardial infarction with stem cell preparations promises to improve myocardial tissue recovery, but this is still limited due to poor accumulation and retention of therapeutic agents at target sites. Cheng et al. [130][55] used MNPs to enhance the targeted delivery of cardiac-derived stem cells (CDCs) in female rats with myocardial infarction. Then, a 1.3 T circular magnet was placed about 1 cm above the apex of the heart for 10 min, starting with an intramuscular injection of CDCs. During this process, the naked eye can see slight discoloration of adjacent tissues, suggesting that magnetic particle-labeled CDCs could prevent coronary washout. After 24 h, histology confirmed the retention of magnetic particle-labeled CDCs. Semi-quantitative fluorescence imaging showed that cells spread more in a subgroup of rats injected with non-magnetic or magnetically labeled CDCs without magnets than in rats that received labeled cells and additional magnetically targeted therapy to their lungs and spleen. Subsequently, the SRY gene that was decisively differentiated was analyzed by polymerase chain reaction (PCR). The results showed that CDCs implantation was three times higher in the myocardial tissue of rats in the magnetic target group. Therefore, the authors concluded that magnetic targeting could effectively attenuate the flushing of magnetic-particle-labeled CDCs at the injection site and significantly increase short-term CDCs engraftment in just 10 min. As targeted carriers, MNPs can effectively participate in the treatment of vascular injury. More applications can also be used as magnetic resonance contrast agents for MRI, which can accurately evaluate vascular functional and structural parameters to diagnose and treat.

4. MNPs as Contrast Agents for Vascular Microenvironment Imaging

Magnetic Resonance Imaging (MRI) is one of the most effective diagnostic imaging tools in medicine, providing clinicians with a high spatial and temporal resolution of biological anatomy and metabolic/functional information in a non-invasive manner. Tissue necrosis, ischemia, and other malignant diseases are of great significance. Under the action of an EMF, different tissues and organs of the organism can generate different resonance signals to form MR images. The strength of the resonance signal is determined by the water content of each part of the body and the relaxation time of water protons. The contrast agent is an image-enhancing contrast agent that can change the body’s relaxation rate of water protons, improve imaging contrast, and display lesions [29,32,131][56][57][58]. MNPs are considered to have promising applications in T2 MRI contrast agents, and especially iron-based MNPs exhibit longer half-lives than clinically used gadolinium-based contrast agents [132] (Figure 6)[59]. At present, a variety of iron-based MNPs have been developed as clinical MRI contrast agents for imaging various tissues. For example, the FDA approved Feridex to detect liver lesions, and Combidex has entered the phase III clinical trial stage for the imaging of lymph node metastasis [133][60]. In terms of vascular structures, in addition to participating in vascular repair in the above ways, MNPs can also be used as vascular microenvironment imaging contrast agents to observe the dynamic changes of vascular graft contour, stenosis or occlusion, and other abnormalities through image visualization to evaluate the process and effect of repair [134][61]. Flores et al. [135][62] demonstrated the feasibility of MRI to assess the in vivo performance of tissue-engineered vascular grafts (TEVG) by labeling human aortic smooth muscle cells (HASMCs) with USPIO nanoparticles, which were then seeded into a TEVG and implanted in mice in vivo. The results showed that USPIO-labeled TEVG consistently had sharper boundaries and lowered T2 relaxation time values than unlabeled control scaffolds. In addition, MNPs labeled cells were also used to observe the behavior of related vascular cells by MRI. Perea et al. [136][63] Labeled HUVECs with clinically approved SPIO, then drove cells to the lumen of polytetrafluoroethylene (PTFE) tubular grafts through a particular electromagnet and then detected endothelial cells with a 1.5 T magnetic resonance scanner to evaluate vascular endothelialization.

5. Other Role of MNPs in Vascular Repair

MNPs are exposed to alternating EMF, which triggers particle movement and local heating, which produces a high-temperature effect that causes tissue damage in the area around the nanoparticles and have been applied to tumor treatment. The main mechanism of action is to raise the temperature above 42 °C through magnetic heating and lead to protein denaturation, which leads to cell death. At present, this method has also been an effective means to treat tumor vascular injury. Higher thermal stimulation based on physiological temperature can effectively kill intravascular tumor cells [137,138][64][65] and inhibit blood flow to promote the recovery of vascular function [139][66]. In recent years, studies have also found that MNPs also have biological effects, such as promoting the polarization of macrophages and producing ROS effects. These effects will also have a significant impact on the vascular repair. Zanganeh et al. [140][67] found that high concentrations of ferumoxytol can promote macrophage polarization to M1, thereby enhancing the regulation of cancer immunotherapy, including breast cancer, liver cancer, and lung cancer. However, some scholars pointed out that a low concentration of MNPs can also promote the growth of blood vessels [101][28]. There is no more evidence to prove whether it may regulate the polarization of macrophages at the injured site to M2 type to promote repair.
MNPs participate in vascular injury repair based on their unique physicochemical properties. However, no matter how it participates in vascular repair, MNPs will pass through the blood circulatory system, affecting the vascular wall’s function, blood pressure, or hemodynamics. The most typical is that when INOPs are less than 7 nm, they will leak out of the vascular structures and be discharged by the kidney, while 200 nm–4 μM particles are easily phagocytized by macrophages of the mononuclear phagocytosis system (MPS). Therefore, the development of INOPs for vascular usually needs to be at 10–200 nm [158,159][68][69]. Secondly, it was known that the endothelial cell layer is the innermost layer of the vascular wall, which can maintain the hemostasis and smooth blood flow of vascular structures by releasing NO, heparin, plasmin, and other regulatory molecules [160,161][70][71]. The instability of INOPs sometimes leads to the release of iron ions, resulting in the dysfunction of most organelles in endothelial cells, such as lysosome, golgi apparatus, endoplasmic reticulum, and mitochondria, which in turn induces oxidative stress, inflammation, and gene mutation, and finally leads to the destruction of the endothelial cell layer, the impairment of vascular wall function, and thrombosis [162]。此外，通常裸露的[72]. In addition, usually naked INOPs 容易在复杂的盐溶液（如血液）中聚集，对活组织或血管结构产生不利影响。稳定的抗聚集涂层，如血清白蛋白，可以大大提高are prone to aggregate in complex saline solutions (such as blood), adversely affecting living tissue or occluding vascular structures. Stable anti-aggregation coatings, such as serum albumin, can greatly improve IONP 的分散性dispersibility [[73][74][75]. 163More importantly, 164studies have shown that the concentration of ions also significantly affects blood ,pressure 165and ]。更重要的是，研究表明离子浓度也会显着影响血压和血流动力学。hemodynamics.

References

  1. Zhuang, Y.; Zhang, C.; Cheng, M.; Huang, J.; Liu, Q.; Yuan, G.; Lin, K.; Yu, H. Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts. Bioact. Mater. 2021, 6, 1791–1809.
  2. Liu, X.; Chen, B.; Li, Y.; Kong, Y.; Gao, M.; Zhang, L.Z.; Gu, N. Development of an electrospun polycaprolactone/silk scaffold for potential vascular tissue engineering applications. J. Bioact. Compat. Polym. 2021, 36, 59–76.
  3. Fukunishi, T.; Ong, C.S.; Yesantharao, P.; Best, C.A.; Yi, T.; Zhang, H.; Mattson, G.; Boktor, J.; Nelson, K.; Shinoka, T.; et al. Different degradation rates of nanofiber vascular grafts in small and large animal models. J. Tissue Eng. Regen. Med. 2020, 14, 203–214.
  4. Zheng, M.; Guo, J.; Li, Q.; Yang, J.; Han, Y.; Yang, H.; Yu, M.; Zhong, L.; Lu, D.; Li, L.; et al. Syntheses and characterization of anti-thrombotic and anti-oxidative Gastrodin-modified polyurethane for vascular tissue engineering. Bioact. Mater. 2021, 6, 404–419.
  5. Tanaka, T.; Tanaka, R.; Ogawa, Y.; Takagi, Y.; Asakura, T. Development of Small-diameter Polyester Vascular Grafts Coated with Silk Fibroin Sponge. Organogenesis 2020, 16, 1–13.
  6. Wang, C.; Zhang, Q.; Uchida, S.; Kodama, M. A new vascular prosthesis coated with polyamino-acid urethane copolymer (PAU) to enhance endothelialization. J. Biomed. Mater. Res. 2002, 62, 315–322.
  7. Cai, Q.; Liao, W.; Xue, F.; Wang, X.; Zhou, W.; Li, Y.; Zeng, W. Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft. Bioact. Mater. 2021, 6, 2557–2568.
  8. Teodorescu, M.; Bercea, M.; Morariu, S. Biomaterials of Poly(vinyl alcohol) and Natural Polymers. Polym. Rev. 2018, 58, 247–287.
  9. Liu, X.; Sun, Y.; Chen, B.; Li, Y.; Zhu, P.; Wang, P.; Yan, S.; Li, Y.; Yang, F.; Gu, N. Novel magnetic silk fibroin scaffolds with delayed degradation for potential long-distance vascular repair. Bioact. Mater. 2022, 7, 126–143.
  10. de Silva, R.; Vongsanga, K.; Wang, X.; Byrne, N. Development of a novel regenerated cellulose composite material. Carbohydr. Polym. 2015, 121, 382–387.
  11. Zhang, L.; Liu, X.; Li, G.; Wang, P.; Yang, Y. Tailoring degradation rates of silk fibroin scaffolds for tissue engineering. J. Biomed. Mater. Res. Part A 2019, 107, 104–113.
  12. Mertens, M.E.; Koch, S.; Schuster, P.; Wehner, J.; Wu, Z.; Gremse, F.; Schulz, V.; Rongen, L.; Wolf, F.; Frese, J.; et al. USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts. Biomaterials 2015, 39, 155–163.
  13. Zhao, Q.; Shi, M.; Yin, C.; Zhao, Z.; Zhang, J.; Wang, J.; Shen, K.; Zhang, L.; Tang, H.; Xiao, Y.; et al. Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis. Nano-Micro Lett. 2021, 13, 28.
  14. Ghorbani, F.; Zamanian, A.; Shams, A.; Shamoosi, A.; Aidun, A. Fabrication and characterisation of super-paramagnetic responsive PLGA–gelatine–magnetite scaffolds with the unidirectional porous structure: A physicochemical, mechanical, and in vitro evaluation. IET Nanobiotechnol. 2019, 13, 860–867.
  15. Lekakou, C.; Lamprou, D.; Vidyarthi, U.; Karopoulou, E.; Zhdan, P. Structural hierarchy of biomimetic materials for tissue engineered vascular and orthopedic grafts. J. Biomed. Mater. Res. Part B Appl. Biomater. 2008, 85B, 461–468.
  16. Mertens, M.E.; Hermann, A.; Bühren, A.; Olde-Damink, L.; Möckel, D.; Gremse, F.; Ehling, J.L.A.; Kiessling, F.; Lammers, T. Iron Oxide-Labeled Collagen Scaffolds for Non-Invasive MR Imaging in Tissue Engineering. Adv. Funct. Mater. 2014, 24, 754–762.
  17. Jaganathan, S.K.; Vellayappan, M.V.; Balaji, A.; Subramanian, A.; John, A.A.; Murugesan, S.; Supriyanto, E.; Yusof, M. Multifaceted prospects of nanocomposites for cardiovascular grafts and stents. Int. J. Nanomed. 2015, 10, 2785–2803.
  18. Tu, Z.; Chen, M.; Wang, M.; Shao, Z.; Jiang, X.; Wang, K.; Yao, Z.; Yang, S.; Zhang, X.; Gao, W.; et al. Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory, Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair. Adv. Funct. Mater. 2021, 31, 2100924.
  19. Witherel, C.E.; Sao, K.; Brisson, B.K.; Han, B.; Volk, S.W.; Petrie, R.J.; Han, L.; Spiller, K.L. Regulation of extracellular matrix assembly and structure by hybrid M1/M2 macrophages. Biomaterials 2021, 269, 120667.
  20. Yan, W.; Li, T.; Yin, T.; Hou, Z.; Qu, K.; Wang, N.; Durkan, C.; Dong, L.; Qiu, J.; Gregersen, H.; et al. M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation. Theranostics 2020, 10, 10712–10728.
  21. Vosen, S.; Rieck, S.; Heidsieck, A.; Mykhaylyk, O.; Zimmermann, K.; Bloch, W.; Eberbeck, D.; Plank, C.; Gleich, B.; Pfeifer, A.; et al. Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets. ACS Nano 2016, 10, 369–376.
  22. Ishii, M.; Shibata, R.; Numaguchi, Y.; Kito, T.; Suzuki, H.; Shimizu, K.; Ito, A.; Honda, H.; Murohara, T. Enhanced Angiogenesis by Transplantation of Mesenchymal Stem Cell Sheet Created by a Novel Magnetic Tissue Engineering Method. Arterioscler. Thromb. Vasc. Biol. 2011, 31, 2210–2215.
  23. Perea, H.; Aigner, J.; Hopfner, U.; Wintermantel, E. Direct Magnetic Tubular Cell Seeding: A Novel Approach for Vascular Tissue Engineering. Cells Tissues Organs 2006, 183, 156–165.
  24. Mattix, B.M.; Olsen, T.R.; Casco, M.; Reese, L.; Poole, J.T.; Zhang, J.; Visconti, R.P.; Simionescu, A.; Simionescu, D.T.; Alexis, F. Janus magnetic cellular spheroids for vascular tissue engineering. Biomaterials 2014, 35, 949–960.
  25. Filippi, M.; Dasen, B.; Guerrero, J.; Garello, F.; Isu, G.; Born, G.; Ehrbar, M.; Martin, I.; Scherberich, A. Magnetic nanocomposite hydrogels and static magnetic field stimulate the osteoblastic and vasculogenic profile of adipose-derived cells. Biomaterials 2019, 223, 119468.
  26. Gu, Z.; Liu, T.; Tang, J.; Yang, Y.; Song, H.; Tuong, Z.K.; Fu, J.; Yu, C. Mechanism of Iron Oxide-Induced Macrophage Activation: The Impact of Composition and the Underlying Signaling Pathway. J. Am. Chem. Soc. 2019, 141, 6122–6126.
  27. Wynn, T.A.; Vannella, K.M. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity 2016, 44, 450–462.
  28. Kargozar, S.; Baino, F.; Hamzehlou, S.; Hamblin, M.R.; Mozafari, M. Nanotechnology for angiogenesis: Opportunities and challenges. Chem. Soc. Rev. 2020, 49, 5008–5057.
  29. Kang, T.; Li, F.; Baik, S.; Shao, W.; Ling, D.; Hyeon, T. Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy. Biomaterials 2017, 136, 98–114.
  30. Osaka, T.; Nakanishi, T.; Shanmugam, S.; Takahama, S.; Zhang, H. Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells. Colloids Surf. B Biointerfaces 2009, 71, 325–330.
  31. Kenzaoui, B.H.; Vila, M.R.; Miquel, J.M.; Cengelli, F.; Juillerat-Jeanneret, L. Evaluation of uptake and transport of cationic and anionic ultrasmall iron oxide nanoparticles by human colon cells. Int. J. Nanomed. 2012, 7, 1275–1286.
  32. Le, T.-A.; Zhang, X.; Hoshiar, A.K.; Yoon, J. Real-Time Two-Dimensional Magnetic Particle Imaging for Electromagnetic Navigation in Targeted Drug Delivery. Sensors 2017, 17, 2050.
  33. Price, P.M.; Mahmoud, W.E.; Al-Ghamd, A.A.; Bronstein, L.M. Magnetic Drug Delivery: Where the Field Is Going. Front. Chem. 2018, 6, 619.
  34. Zhang, L.K.; Du, S.; Wang, X.; Jiao, Y.; Yin, L.; Zhang, Y.; Guan, Y.-Q. Bacterial cellulose based composites enhanced transdermal drug targeting for breast cancer treatment. Chem. Eng. J. 2019, 370, 749–759.
  35. Zhang, L.; Qin, Z.; Sun, H.; Chen, X.; Dong, J.; Shen, S.; Zheng, L.; Gu, N.; Jiang, Q. Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment. Bioact. Mater. 2022, 18, 1–14.
  36. Wang, S.; Guo, X.; Ren, L.; Wang, B.; Hou, L.; Zhou, H.; Gao, Q.; Gao, Y.; Wang, L. Targeting and deep-penetrating delivery strategy for stented coronary artery by magnetic guidance and ultrasound stimulation. Ultrason. Sonochem. 2020, 67, 105188.
  37. Su, C.H.; Li, W.-P.; Tsao, L.-C.; Wang, L.-C.; Hsu, Y.-P.; Wang, W.-J.; Liao, M.-C.; Lee, C.-L.; Yeh, C.-S. Enhancing Microcirculation on Multitriggering Manner Facilitates Angiogenesis and Collagen Deposition on Wound Healing by Photoreleased NO from Hemin-Derivatized Colloids. ACS Nano 2019, 13, 4290–4301.
  38. Chorny, M.; Fishbein, I.; Forbes, S.; Alferiev, I. Magnetic nanoparticles for targeted vascular delivery. IUBMB Life 2011, 63, 613–620.
  39. de la Ossa, N.P.; Carrera, D.; Gorchs, M.; Querol, M.; Millán, M.; Gomis, M.; Dorado, L.; López-Cancio, E.; Hernández-Pérez, M.; Chicharro, V.; et al. Design and Validation of a Prehospital Stroke Scale to Predict Large Arterial Occlusion the Rapid Arterial Occlusion Evaluation Scale. Stroke 2014, 45, 87–91.
  40. Loenneke, J.P.; Fahs, C.A.; Rossow, L.M.; Sherk, V.D.; Thiebaud, R.S.; Abe, T.; Bemben, D.A.; Bemben, M.G. Effects of cuff width on arterial occlusion: Implications for blood flow restricted exercise. Eur. J. Appl. Physiol. 2012, 112, 2903–2912.
  41. Heiferman, D.M.; Li, D.D.; Pecoraro, N.C.; Smolenski, A.M.; Tsimpas, A.; Ashley, W.W. Intra-Arterial Alteplase Thrombolysis during Mechanical Thrombectomy for Acute Ischemic Stroke. J. Stroke Cerebrovasc. Dis. 2017, 26, 3004–3008.
  42. Dalzotto, K.; Richards, P.; Boulter, T.D.; Kay, M.; Mititelu, M. Complications of Intra-Arterial tPA for Iatrogenic Branch Retinal Artery Occlusion: A Case Report through Multimodal Imaging and Literature Review. Medicina 2021, 57, 963.
  43. Cicha, I.; Alexiou, C. Cardiovascular applications of magnetic particles. J. Magn. Magn. Mater. 2021, 518, 167428.
  44. Ma, Y.-H.; Wu, S.-Y.; Wu, T.; Chang, Y.-J.; Hua, M.-Y.; Chen, J.-P. Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles. Biomaterials 2009, 30, 3343–3351.
  45. Schachter, M. The pathogenesis of atherosclerosis. Int. J. Cardiol. 1997, 62, S3–S7.
  46. Mannarino, E.; Pirro, M. Endothelial Injury and Repair: A Novel Theory for Atherosclerosis. Angiology 2008, 59, 69S–72S.
  47. Luo, N.; Fang, J.; Wei, L.; Sahebkar, A.; Little, P.J.; Xu, S.; Luo, C.; Li, G. Emodin in atherosclerosis prevention: Pharmacological actions and therapeutic potential. Eur. J. Pharmacol. 2021, 890, 173617.
  48. Song, L.; Zhang, J.; Lai, R.; Li, Q.; Ju, J.; Xu, H. Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis. Front. Pharmacol. 2021, 12, 675999.
  49. Ji, C.; Yi, H.; Huang, J.; Zhang, W.; Zheng, M. Propofol alleviates inflammation and apoptosis in HCY-induced HUVECs by inhibiting endoplasmic reticulum stress. Mol. Med. Rep. 2021, 23, 333.
  50. Cicha, I.; Matuszak, J.; Lutz, B.; Alexiou, C.; Lyer, S. Magnetic drug targeting to vascular injury regions and atherosclerotic lesions: In vivo pilot study. Eur. Heart J. 2018, 39, 801.
  51. Carrillo-Jimenez, R.; Houser, S.L.; Jaffer, F.A. Culprit lesion atherothrombectomy during acute myocardial infarction—Extraction of an acute coronary plaque rupture. Circulation 2005, 112, E267.
  52. Baghdasaryan, P.; Natarajan, B.; Nalbandian, M.; Varadarajan, P.; Pai, R.G. Myocardial Infarction with Nonobstructive Coronary Artery Disease-Definition, Etiopathogenesis, Diagnosis, and Management. Int. J. Angiol. 2021.
  53. Wereski, R.; Kimenai, D.M.; Bularga, A.; Taggart, C.; Lowe, D.J.; Mills, N.L.; Chapman, A.R. Risk factors for type 1 and type 2 myocardial infarction. Eur. Heart J. 2021, 43, 127–135.
  54. Zhang, Y.; Li, W.; Ou, L.; Wang, W.; Delyagina, E.; Lux, C.; Sorg, H.; Riehemann, K.; Steinhoff, G.; Ma, N. Targeted Delivery of Human VEGF Gene via Complexes of Magnetic Nanoparticle-Adenoviral Vectors Enhanced Cardiac Regeneration. PLoS ONE 2012, 7, e39490.
  55. Cheng, K.; Li, T.-S.; Malliaras, K.; Davis, D.R.; Zhang, Y.; Marbán, E. Magnetic Targeting Enhances Engraftment and Functional Benefit of Iron-Labeled Cardiosphere-Derived Cells in Myocardial Infarction. Circ. Res. 2010, 106, 1570–1581.
  56. Dadfar, S.M.; Roemhild, K.; Drude, N.I.; von Stillfried, S.; Knüchel, R.; Kiessling, F.; Lammers, T. Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications. Adv. Drug Deliv. Rev. 2019, 138, 302–325.
  57. Magro, M.; Baratella, D.; Bonaiuto, E.; de Almeida Roger, J.; Vianello, F. New Perspectives on Biomedical Applications of Iron Oxide Nanoparticles. Curr. Med. Chem. 2018, 25, 540–555.
  58. Huang, Y.; Hsu, J.C.; Koo, H.; Cormode, D.P. Repurposing ferumoxytol: Diagnostic and therapeutic applications of an FDA-approved nanoparticle. Theranostics 2022, 12, 796–816.
  59. Toth, G.B.; Varallyay, C.G.; Horvath, A.; Bashir, M.R.; Choyke, P.L.; Daldrup-Link, H.E.; Dosa, E.; Finn, J.P.; Gahramanov, S.; Harisinghani, M.; et al. Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Kidney Int. 2017, 92, 47–66.
  60. Woo, K.; Lee, H.; Ahn, J.-P.; Park, Y. Sol–Gel Mediated Synthesis of Fe2O3 Nanorods. Adv. Mater. 2003, 15, 1761–1764.
  61. Bremerich, J.; Bilecen, D.; Reimer, P. MR angiography with blood pool contrast agents MR angiography with blood pool contrast agents. Eur. Radiol. 2007, 17, 3017–3024.
  62. Flores, D.; Yu, X. Innovative Tissue-Engineered and Synthetic Vascular Graft Models for the Treatment of PAD in Small-Diameter Arteries. Regen. Eng. Transl. Med. 2017, 3, 215–223.
  63. Perea, H.; Aigner, J.; Heverhagen, J.T.; Hopfner, U.; Wintermantel, E. Vascular tissue engineering with magnetic nanoparticles: Seeing deeper. J. Tissue Eng. Regen. Med. 2007, 1, 318–321.
  64. Senthilkumar, N.; Sharma, P.K.; Sood, N.; Bhalla, N. Designing magnetic nanoparticles for in vivo applications and understanding their fate inside human body. Coord. Chem. Rev. 2021, 445, 214082.
  65. Lemine, O.M. Chapter 7—Magnetic Hyperthermia Therapy Using Hybrid Magnetic Nanostructures. In Hybrid Nanostructures for Cancer Theranostics; Ashok Bohara, R., Thorat, N., Eds.; Elsevier: Amsterdam, The Netherlands, 2019; pp. 125–138.
  66. Wang, Q.; Deng, Z.S.; Liu, J. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia. J. Nanopart. Res. 2012, 14, 974.
  67. Zanganeh, S.; Hutter, G.; Spitler, R.; Lenkov, O.; Mahmoudi, M.; Shaw, A.; Pajarinen, J.S.; Nejadnik, H.; Goodman, S.; Moseley, M.; et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotechnol. 2016, 11, 986–994.
  68. Zhao, J.; Gao, W.; Cai, X.; Xu, J.; Zou, D.; Li, Z.; Hu, B.; Zheng, Y. Nanozyme-mediated catalytic nanotherapy for inflammatory bowel disease. Theranostics 2019, 9, 2843–2855.
  69. Zhao, J.; Cai, X.; Gao, W.; Zhang, L.; Zou, D.; Zheng, Y.; Li, Z.; Chen, H. Prussian Blue Nanozyme with Multienzyme Activity Reduces Colitis in Mice. ACS Appl. Mater. Interfaces 2018, 10, 26108–26117.
  70. Otsuka, F.; Finn, A.V.; Yazdani, S.K.; Nakano, M.; Kolodgie, F.D.; Virmani, R. The importance of the endothelium in atherothrombosis and coronary stenting. Nat. Rev. Cardiol. 2012, 9, 439–453.
  71. Jana, S. Endothelialization of cardiovascular devices. Acta Biomater. 2019, 99, 53–57.
  72. Wang, Y.; Santos, A.; Evdokiou, A.; Losic, D. An overview of nanotoxicity and nanomedicine research: Principles, progress and implications for cancer therapy. J. Mater. Chem. B 2015, 3, 7153–7172.
  73. Hajshafiei, P.; Fatahian, S.; Shahanipoor, K. In vivo toxicity assessment of bovine serum albumin and dimercaptosuccinic acid. coated Fe3O4 nanoparticles. Iran. J. Biotechnol. 2014, 12, e16858.
  74. Khatiri, R.; Reyhani, A.; Mortazavi, S.Z.; Hossainalipour, M. Immobilization of serum albumin on the synthesized three layers core-shell structures of super-paramagnetic iron oxide nanoparticles. J. Ind. Eng. Chem. 2013, 19, 1642–1647.
  75. Ramesh, R.; Ponnusamy, S.; Muthamizhchelvan, C. Synthesis, properties and heating characteristics of bovine serum albumin coated Fe3O4 magnetic fluid for magnetic fluid hyperthermia application. Sci. Adv. Mater. 2013, 5, 1250–1255.
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