biomimetic nanoparticle

仿生纳米粒子
  • 文章类型: Journal Article
    光热疗法(PTT),它利用光热剂的高热转化能力在高温下消融肿瘤细胞,由于其具有高选择性和特异性等优点,精确靶向肿瘤部位,低侵袭性和创伤。然而,由NIR-I引导的PTT在组织穿透深度方面具有局限性,导致对深部肿瘤组织的影像学监测和治疗效果有限。此外,在治疗过程中,纳米粒子容易被免疫系统清除,难以被动靶向肿瘤部位。为了解决这些问题,我们使用NIR-II染料IR1048和DSPE-PEG-OH制备了纳米颗粒,并将它们进一步包裹在小鼠的红细胞膜中。这些仿生纳米粒子,称为RDIR1048,显示免疫系统的清除率降低,并具有长循环特征。它们有效地积累在肿瘤部位,给药后96小时,在肿瘤部位仍可观察到强烈的荧光。此外,通过小鼠热成像实验,我们发现RDIR1048表现出良好的PTT能力。当与免疫检查点抑制剂联合使用时,抗PD-L1抗体,它增强了由PTT引起的肿瘤细胞的免疫原性细胞死亡,提高了免疫治疗的治疗效果,在荷瘤小鼠的治疗中表现出良好的治疗效果。本研究为今后开发具有长环流性质的NIR-Ⅱ纳米粒子提供了可行的依据。
    Photothermal therapy (PTT), which uses the high thermal conversion ability of photothermal agents to ablate tumor cells at high temperatures, has gained significant attention because it has the advantages of high selectivity and specificity, precise targeting of tumor sites, and low invasiveness and trauma. However, PTT guided by the NIR-I has limitations in tissue penetration depth, resulting in limited imaging monitoring and therapeutic effects on deep-seated tumor tissues. Moreover, nanoparticles are easily cleared by the immune system and difficult to passively target tumor sites during the process of treatment. To address these issues, we prepared nanoparticles using NIR-II dyes IR1048 and DSPE-PEG-OH and further encapsulated them in red blood cell membranes derived from mice. These biomimetic nanoparticles, called RDIR1048, showed reduced clearance by the immune system and had long circulation characteristics. They effectively accumulated at tumor sites, and strong fluorescence could still be observed at the tumor site 96 h after administration. Furthermore, through mouse thermal imaging experiments, we found that RDIR1048 exhibited good PTT ability. When used in combination with an immune checkpoint inhibitor, anti-PD-L1 antibodies, it enhanced the immunogenic cell death of tumor cells caused by PTT and improved the therapeutic effect of immunotherapy, which demonstrated good therapeutic efficacy in the treatment of tumor-bearing mice. This study provides a feasible basis for the future development of NIR-II nanoparticles with long circulation properties.
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  • 文章类型: Journal Article
    动脉粥样硬化斑块表现出高胆固醇沉积和由高活性氧(ROS)引起的氧化应激。这些是斑块中的主要成分和主要的促炎因子。因此,制定有效的治疗策略至关重要,该策略可以通过去除胆固醇和抑制过度积累的ROS同时解决多种促炎因子。在这项研究中,我们构建了巨噬细胞膜包裹的仿生纳米颗粒(MM@DA-pCD@MTX),它不仅通过反向胆固醇转运减轻斑块病变处的胆固醇沉积,而且清除过度积累的ROS。β-环糊精(β-CD)和负载的甲氨蝶呤(MTX)协同作用以诱导胆固醇流出,以抑制泡沫细胞的形成。其中,MTX上调ABCA1、CYP27A1和SR-B1的表达。β-CD增加了胆固醇晶体的溶解度。此外,多巴胺(DA)的ROS清除特性在MM@DA-pCD@MTX中得到了完美的保留,可以清除过度积累的ROS以减轻斑块病变处的氧化应激。最后但并非最不重要的,MM功能化的“归巢”靶向动脉粥样硬化斑块不仅可以靶向给药,而且可以延长体内循环时间和药物半衰期。总之,MM@DA-pCD@MTX成为一种有效的,用于AS治疗的多功能治疗平台,在解决动脉粥样硬化的复杂病理生理学方面提供高度的生物安全性和有效性。
    Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized \"homing\" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.
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  • 文章类型: Journal Article
    输血每天都能挽救生命并改善健康。尽管血型匹配比以往任何时候都更严格,当接受者缺乏可接受的血型时,在临床上仍然不可避免地进行不相容血型的紧急输血。为了克服这一点,开发了一种由涂覆有红细胞(RBC)膜的聚合物核组成的计数器纳米平台。用A型或B型红细胞膜伪装,纳米平台能够在B型或A型全血中特异性捕获抗A或抗BIgM抗体,从而降低相应的IgM抗体水平,然后允许不相容的输血。除了IgM,被动免疫小鼠模型中的抗RBCIgG抗体同样可以被该纳米平台中和,导致不相容供体红细胞的循环时间延长。值得注意的是,由过期的RBC(低温储存>42天)制备并随后进行冻干的纳米平台不损害其对抗体中和的作用。最重要的是,抗体捕获的RBC-NP不会加剧炎症的风险,补体激活,急性失血性休克小鼠模型的凝血障碍。总的来说,这种仿生纳米平台可以安全地中和抗体,使不相容的输血。
    Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)是全球癌症相关死亡的第四大原因。除了早期发现,早期诊断,和早期手术,迫切需要尝试治疗HCC的新策略。雷公藤甲素(TPL)已用于治疗HCC。然而,其临床应用受到治疗窗口狭窄的限制,严重毒性,水溶性差。在这项研究中,我们开发了具有同源靶向特性的加载TPL(TPL@mPLGA)的癌细胞膜伪装仿生PLGA纳米颗粒,用于治疗HCC。成功制备了粒径为195.5±7.5nm、zeta电位为-21.5±0.2mV、稳定性良好的TPL@mPLGA。TPL@mPLGA的载药量(DL)为2.94%。Huh-7细胞膜涂层后,发现天然的Huh-7细胞膜蛋白保留在TPL@mPLGA上,因此TPL@mPLGA在肿瘤部位的积累增强,与TPL或TPL@PLGA相比,体内外抗肿瘤活性更好。TPL@mPLGA显示出增强的抗肿瘤作用和降低的毒性,可用于肝癌的治疗。
    Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.
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  • 文章类型: Journal Article
    类风湿性关节炎(RA)是一种全身性免疫疾病,对关节健康具有严重影响。非特异性药物分布的问题潜在地限制了治疗功效并增加了与RA治疗相关的风险。研究人员采用细胞膜包被的仿生纳米颗粒(NPs)来增强靶向递送功效,以满足受影响关节内药物积累的需求。此外,不同的细胞膜提供独特的功能,如免疫细胞活化和增强NP生物相容性。在这次审查中,详细总结了当前的RA治疗策略,然后概述了RA的发病机理和产生细胞膜涂层仿生NPs的方法。探索各种细胞来源的细胞膜仿生NPs在RA治疗中的应用。突出了单个细胞膜的独特属性以及杂化膜构型。通过对细胞膜仿生NPs的全面评估,我们阐明了RA治疗领域的未来应用和挑战,并提出了综合治疗的策略。在未来,细胞膜仿生NPs对RA具有广阔的治疗前景。
    Rheumatoid arthritis (RA) is a systemic immune disease with severe implications for joint health. The issue of non-specific drug distribution potentially limits the therapeutic efficacy and increases the risk associated with RA treatment. Researchers employed cytomembrane-coated biomimetic nanoparticles (NPs) to enhance the targeting delivery efficacy to meet the demand for drug accumulation within the affected joints. Furthermore, distinct cytomembranes offer unique functionalities, such as immune cell activation and augmented NP biocompatibility. In this review, the current strategies of RA treatments were summarized in detail, and then an overview of RA\'s pathogenesis and the methodologies for producing cytomembrane-coated biomimetic NPs was provided. The application of cytomembrane biomimetic NPs derived from various cell sources in RA therapy is explored, highlighting the distinctive attributes of individual cytomembranes as well as hybrid membrane configurations. Through this comprehensive assessment of cytomembrane biomimetic NPs, we elucidate the prospective applications and challenges in the realm of RA therapy, and the strategy of combined therapy is proposed. In the future, cytomembrane biomimetic NPs have a broad therapeutic prospect for RA.
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  • 文章类型: Journal Article
    鼻咽癌(NPC)是一种常见的头颈部恶性肿瘤,其特点是发病率高,攻击性强,诊断差,治疗机会有限。实现精确的NPC主动靶向药物递送的创新策略已成为临床研究的突出焦点。这里,设计了一种极简主义的癌细胞膜(CCM)屏蔽仿生纳米粒子(NP),用于NPC主动靶向治疗.将化学疗法模型药物阿霉素(DOX)装载在聚酰胺胺(PAMAM)树枝状聚合物中。PAMAM/DOX(PD)NP进一步被人CNE-2NPCCCM屏蔽。表征结果表明,仿生PAMAM/DOX@CCM(简称PDC)NPs具有令人满意的物理特性,具有高DOX负载和出色的稳定性。细胞实验表明,CNE-2膜遮盖的PDCNP通过同源靶向和粘附相互作用在来源细胞中呈现强大的细胞摄取。进一步的体内结果证实,这种仿生纳米平台具有延长的循环和显着的肿瘤靶向能力,和PDCNP通过全身给药有效抑制CNE-2肿瘤的进展。这种CCM屏蔽的仿生NP展示了一种用于精确NPC治疗的极简范式纳米平台,CCM屏蔽仿生药物递送系统(DDS)的策略在广泛的癌症主动靶向治疗中具有巨大的潜力。
    Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.
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  • 文章类型: Journal Article
    肺中的细胞因子风暴和ROS过量产生总是在很短的时间内导致急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)。有效控制细胞因子风暴释放综合征(CRS)和清除ROS是ALI/ARDS防治的关键。在这项工作中,采用乳化蒸发法制备柚皮苷纳米颗粒(Nar-NPs),提取间充质干细胞膜(CM),并通过手工挤压法包被在Nar-NP表面,获得仿生CM@Nar-NP。体外,CM@Nar-NP表现出良好的分散性,优异的生物相容性,和生物安全。在细胞层面,CM@Nar-NP具有优异的靶向发炎巨噬细胞的能力和清除ROS的能力。体内成像表明,CM@Nar-NP可以靶向并积聚在炎性肺中。在ALI小鼠模型中,气管内(i.t.)滴注CM@Nar-NP显着降低了ROS水平,抑制促炎细胞因子,显著提高了生存率。此外,CM@Nar-NP增加了M2标志物(CD206)的表达,并降低了M1标记(F4/80)在脓毒症小鼠中的表达,表明Nar调节的巨噬细胞向M2亚型极化。总的来说,这项工作证明,基于间充质干细胞膜的仿生纳米颗粒递送系统可以通过i.t.给药有效地靶向肺部炎症;释放的有效载荷抑制炎症细胞因子和ROS的产生,和Nar调节的巨噬细胞向M2表型极化,这可能有助于它们的抗炎作用。这种纳米系统提供了出色的肺炎治疗平台,具有令人满意的生物安全性,并且具有有效提供草药的巨大潜力。
    Cytokine storm and ROS overproduction in the lung always lead to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a very short time. Effectively controlling cytokine storm release syndrome (CRS) and scavenging ROS are key to the prevention and treatment of ALI/ARDS. In this work, the naringin nanoparticles (Nar-NPs) were prepared by the emulsification and evaporation method; then, the mesenchymal stem cell membranes (CMs) were extracted and coated onto the surface of the Nar-NPs through the hand extrusion method to obtain the biomimetic CM@Nar-NPs. In vitro, the CM@Nar-NPs showed good dispersity, excellent biocompatibility, and biosafety. At the cellular level, the CM@Nar-NPs had excellent abilities to target inflamed macrophages and the capacity to scavenge ROS. In vivo imaging demonstrated that the CM@Nar-NPs could target and accumulate in the inflammatory lungs. In an ALI mouse model, intratracheal (i.t.) instillation of the CM@Nar-NPs significantly decreased the ROS level, inhibited the proinflammatory cytokines, and remarkably promoted the survival rate. Additionally, the CM@Nar-NPs increased the expression of M2 marker (CD206), and decreased the expression of M1 marker (F4/80) in septic mice, suggesting that the Nar-modulated macrophages polarized towards the M2 subtype. Collectively, this work proves that a mesenchymal stem cell membrane-based biomimetic nanoparticle delivery system could efficiently target lung inflammation via i.t. administration; the released payload inhibited the production of inflammatory cytokines and ROS, and the Nar-modulated macrophages polarized towards the M2 phenotype which might contribute to their anti-inflammation effects. This nano-system provides an excellent pneumonia-treated platform with satisfactory biosafety and has great potential to effectively deliver herbal medicine.
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  • 文章类型: Journal Article
    由于其固有的膜结构,由活性细胞膜包裹的纳米结构具有独特的特征,例如在血液中长时间存在,精确的识别能力,和逃避免疫反应。这项研究涉及仿生纳米粒子的生产,特别是负载有甲氨蝶呤(MTX)的中空金纳米颗粒(HGNPs),进一步涂有癌细胞膜。然后用AS1411适体装饰这些纳米颗粒以用作靶向剂(Apt-CCM-HG@MTX)。由于其双重靶向特性(AS1411适体和C26癌细胞膜),纳米平台表现出对癌细胞的精确靶向。表现出分布的均匀性。它还显示了对光热刺激的理想反应,药物的控释,和特殊的荧光成像性能。该系统由直径为51.33±5.70nm的球形HGNP组成,使用物理吸收方法有效地加载了MTX。获得的包封效率记录为79.54%,加载效率达到38.21%。靶向制剂在核仁素阳性细胞系中表现出显著的约45%的死亡率。C26,如通过体外细胞毒性测定所确定的。由于应用于癌细胞膜中发现的同源结合粘附分子的功能化过程和AS1411适体的靶向能力,在体内实验期间,Apt-CCM-HG@MTX在靶向肿瘤和促进细胞摄取方面表现出显著增强。此外,在NIR辐射下,由于HGNP的独特属性,Apt-CCM-HG@MTX在肿瘤区域表现出的光热效应非常强大。从这项研究中获得的结论有可能有助于采用生物启发策略,该策略将显着改善对结直肠癌患者的MTX和治疗的有效管理。
    Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer.
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  • 文章类型: Journal Article
    纳米封装已成为药物递送的最新进展,增强稳定性,生物利用度,并实现受控,靶向物质递送到特定细胞或组织。然而,传统的纳米颗粒递送面临着循环时间短和免疫识别等挑战。为了解决这些问题,细胞膜包被的纳米颗粒已被建议作为一种实用的替代品。生产过程涉及三个主要阶段:细胞裂解和膜破碎,膜隔离,和纳米粒子涂层。通常使用均质化或超声处理的低渗裂解将细胞膜片段化。通过多个离心步骤分离随后的膜片段。纳米粒子涂层可以通过挤出实现,超声处理,或两种方法的组合。值得注意的是,这一分析揭示了缺乏一种普遍适用的纳米粒子涂层方法,因为这三个阶段在程序上有很大不同。这篇综述探讨了细胞膜涂层纳米粒子的当前发展和方法,突出了它们作为靶向药物递送和各种治疗应用的有效替代方案的潜力。
    Nanoencapsulation has become a recent advancement in drug delivery, enhancing stability, bioavailability, and enabling controlled, targeted substance delivery to specific cells or tissues. However, traditional nanoparticle delivery faces challenges such as a short circulation time and immune recognition. To tackle these issues, cell membrane-coated nanoparticles have been suggested as a practical alternative. The production process involves three main stages: cell lysis and membrane fragmentation, membrane isolation, and nanoparticle coating. Cell membranes are typically fragmented using hypotonic lysis with homogenization or sonication. Subsequent membrane fragments are isolated through multiple centrifugation steps. Coating nanoparticles can be achieved through extrusion, sonication, or a combination of both methods. Notably, this analysis reveals the absence of a universally applicable method for nanoparticle coating, as the three stages differ significantly in their procedures. This review explores current developments and approaches to cell membrane-coated nanoparticles, highlighting their potential as an effective alternative for targeted drug delivery and various therapeutic applications.
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  • 文章类型: Journal Article
    急性肝衰竭(ALF)是一种罕见且严重的疾病,其特征是主要的肝细胞死亡和肝功能障碍。由于治疗选择有限,这种疾病通常预后差,死亡率高。当ALF不能通过药物逆转时,经常需要肝移植。然而,移植排斥和供体器官短缺仍然是主要挑战。最近,干细胞疗法已成为治疗肝脏疾病的有希望的替代方法。然而,有限的细胞递送途径和不良的活细胞产品的稳定性极大地阻碍了干细胞疗法的可行性和治疗效果。受间充质干细胞(MSCs)功能的启发,主要通过分泌多种因子,我们开发了一种受MSC启发的仿生多功能纳米框架(MBN),该框架通过与亲水性或疏水性药物组合来封装MSC分泌的生长促进因子。用MBN包被红细胞(RBC)膜以增强其免疫耐受并延长其在血液中的循环时间。重要的是,MBN可以响应氧化微环境,在那里它积累和降解以释放有效载荷。在这项工作中,两种仿生纳米粒子,即,大黄酸包裹的MBN(RMBN)和N-乙酰半胱氨酸(NAC)包裹的MBN(NMBN),被设计和合成。在脂多糖(LPS)/d-半乳糖胺(D-GalN)诱导和对乙酰氨基酚(APAP)诱导的ALF小鼠模型中,RMBN和NMBN可以有效靶向肝脏病变,缓解ALF的急性症状,并通过其强大的抗氧化作用促进肝细胞再生,抗炎,和再生活动。这项研究证明了使用MSC启发的仿生纳米框架治疗ALF的可行性。
    Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.
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