Active targeting

主动靶向
  • 文章类型: Journal Article
    炎症性肠病(IBD)是一种慢性,以肠粘膜反复发炎为特征的非特异性炎症。然而,现有的IBD治疗无效且具有严重的副作用。IBD的病因是多因素的,包括免疫,遗传,环境,饮食,和微生物因素。随着纳米技术的发展,基于特定靶向方法开发的纳米颗粒(NP)显示出巨大的潜力。纳米颗粒被定义为尺寸在1和100nm之间的颗粒。根据它们的尺寸和表面功能,NP表现出不同的性质。多种纳米颗粒类型已被用作治疗炎症性肠病(IBD)的药物载体。在实验模型中观察到令人鼓舞的结果。它们增加了药物的生物利用度,并实现了靶向药物递送,促进局部治疗,从而提高疗效。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。
    Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.
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  • 文章类型: Journal Article
    免疫疗法已经成为对抗肺癌的有力武器,然而,只有一小部分患者对治疗有积极反应。聚(I:C)有效地触发先天和适应性免疫。它还能够在肿瘤细胞中诱导免疫原性细胞死亡(ICD)。然而,其功效受到其体内不稳定性和有限细胞摄取的阻碍。为了解决这个问题,我们将聚(I:C)封装在cRGD靶向聚合物囊泡(t-PPIC)中,显著增加了它的稳定性和吸收,导致树突状细胞(DC)的重要激活和肺肿瘤细胞的凋亡。在鼠LLC肺肿瘤模型中,全身给药t-PPIC可有效抑制肿瘤生长,并带来显著的生存益处,40%的小鼠变得无肿瘤。值得注意的是,t-PPIC在肿瘤组织中引起更强的凋亡和ICD,并引起更有效的DC刺激,NK细胞的募集,激活CD8+T细胞,与游离聚(I:C)和非靶向PPIC对照相比。此外,当与免疫检查点抑制剂或放疗联合使用时,t-PPIC放大了抗肿瘤免疫反应,导致60%的小鼠完全消退。这些令人信服的发现强调了整合素靶向的聚合物体poly(I:C)通过同时诱导ICD和全身免疫激活来增强抗肿瘤免疫力的潜力。本文受版权保护。保留所有权利。
    Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond to the treatment. Poly(I:C) (PIC) effectively triggers both innate and adaptive immunity. It can also induce immunogenic cell death (ICD) in tumor cells. However, its efficacy is hindered by its instability in vivo and limited cellular uptake. To address this, PIC is encapsulated in cRGD-functionalized polymersomes (t-PPIC), which significantly increases its stability and uptake, thus activating dendritic cells (DCs) and inducing apoptosis of lung tumor cells in vitro. In a murine LLC lung tumor model, systemic administration of t-PPIC effectively suppresses tumor growth and leads to survival benefits, with 40% of the mice becoming tumor-free. Notably, t-PPIC provokes stronger apoptosis and ICD in tumor tissue and elicits a more potent stimulation of DCs, recruitment of natural killer (NK) cells, and activation of CD8+ T cells, compared to free PIC and nontargeted PPIC controls. Furthermore, when combined with immune checkpoint inhibitors or radiotherapy, t-PPIC amplifies the antitumor immune response, resulting in complete regression in 60% of the mice. These compelling findings underscore the potential of integrin-targeted polymersomal PIC to enhance antitumor immunity by simultaneously inducing ICD and systemic immune activation.
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  • 文章类型: Journal Article
    玉米醇溶蛋白是来自玉米的主要植物蛋白。近年来,玉米醇溶蛋白已被广泛用于制药,农业,食物,环境保护,和其他领域,因为它具有优异的生物相容性和生物安全性。然而,目前尚缺乏对玉米醇溶蛋白纳米递送系统的系统评价和研究。本文系统综述了玉米醇溶蛋白纳米传递系统的制备和改性方法,基于Zein的基本性质。详细论述了玉米醇溶蛋白纳米粒的制备及其影响因素,以及分析不同制备方法的优缺点,总结玉米醇溶蛋白纳米粒子的改性方法。本研究为玉米醇溶蛋白基纳米传递系统的研究提供了新的思路,促进了其应用。
    Zein is the main vegetable protein from maize. In recent years, Zein has been widely used in pharmaceutical, agriculture, food, environmental protection, and other fields because it has excellent biocompatibility and biosafety. However, there is still a lack of systematic review and research on Zein-based nano-delivery systems. This paper systematically reviews preparation and modification methods of Zein-based nano-delivery systems, based on the basic properties of Zein. It discusses the preparation of Zein nanoparticles and the influencing factors in detail, as well as analyzing the advantages and disadvantages of different preparation methods and summarizing modification methods of Zein nanoparticles. This study provides a new idea for the research of Zein-based nano-delivery system and promotes its application.
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  • 文章类型: Journal Article
    癌症是导致世界上所有国家死亡的严重疾病。基于纳米的药物递送方法是最好的选择,直接靶向肿瘤细胞,改善药物细胞摄取。不同类型的基于纳米颗粒的药物载体用于治疗癌症,提高癌症治疗的有效性和安全性,许多物质已被视为药物载体。最近,基于脂质的纳米颗粒(LBNP)引起了人们的极大兴趣。这些与其他聚合物交替的天然生物分子由于其两亲性质而经常在医学中再循环。脂质纳米颗粒通常提供各种益处,包括生物相容性和生物降解性。这篇综述涵盖了不同类别的LBNP,包括它们的表征和不同的合成技术。这篇综述讨论了脂质纳米颗粒技术的最重要进展及其在药物管理中的应用。此外,该综述还强调了脂质纳米颗粒在不同癌症治疗类型中的应用。
    Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.
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  • 文章类型: Journal Article
    三阴性乳腺癌(TNBC)是一种高度侵袭性和罕见的乳腺癌亚型,预后不良。至关重要的是优先考虑创建高度选择性和主动靶向TNBC的纳米治疗方法。这项研究探索了一种新的纳米系统,Cu9S8-SNAP@PM(C-S@P),由涂覆有血小板膜(PM)的Cu9S8-SNAP组成。该纳米系统的目的是使用多模式疗法治疗TNBC。利用PM包覆的纳米粒子(NPs)能够实现主动靶向,导致C-S@P在肿瘤内的有效积累。这些NP内的Cu9S8组分具有发挥光热疗法(PTT)和化学动力学疗法(CDT)的潜力。同时,S-亚硝基-N-乙酰香草胺(SNAP)成分使一氧化氮(NO)气体治疗(GT)。此外,当暴露于NIR-II激光时,Cu9S8不仅增加了PTT肿瘤区域的温度,但也提高CDT和刺激释放NO通过热反应,以提高GT的有效性。体外和体内实验结果均验证了C-S@P表现出最小的副作用,并代表了靶向肿瘤以进行有效治疗的多功能纳米药物。这种方法有望为TNBC治疗和在肿瘤学中更广泛的应用带来巨大的潜力。
    Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.
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  • 文章类型: Journal Article
    受体和配体结合介导的靶向药物递送系统(DDS)有时无法靶向肿瘤部位,和癌细胞膜(CCM)涂层可以克服体内免疫清除和DDS非特异性结合的困境。为了增强靶向能力,提高抗肿瘤效果,基于U87MGCCM介导的同源靶向和环肽RGD介导的主动靶向,树立了双靶向DDS。通过将掺杂RGD的CCM包被到装载多柔比星(DOX)的脂质体上来制备DDS。同源和主动双重靶向能力赋予DDS(RGD-CCM-LP-DOX)表现出优越的癌细胞亲和力,改善组织分布,增强抗肿瘤作用。体内药效学研究表明,与同源靶向CCM-LP-DOX和非靶向LP-DOX注射相比,RGD-CCM-LP-DOX表现出更好的治疗效果。H&E染色,Ki一67染色和TUNEL染色证实RGD-CCM-LP-DOX不只增加抗肿瘤疗效,而且还通过改变体内分布来降低组织毒性。实验结果表明,掺杂RGD的CCM伪装脂质体DDS是化疗药物递送的较好选择。
    Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.
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  • 文章类型: Journal Article
    光动力疗法(PDT)是目前采用的癌症治疗的合适替代方案。然而,大多数光敏剂的疏水性(例如,锌酞菁(ZnPC))导致它们在血液中聚集。此外,在皮肤中的非特异性积累和低清除率的ZnPC导致持久的皮肤光敏化,迫使预期寿命较短的患者留在室内。因此,这些光敏剂的临床应用是有限的。这里,研究了包封ZnPC(ZnPC-M)的苄基-聚(ε-己内酯)-b-聚(乙二醇)胶束,以增加ZnPC的溶解度及其对癌细胞的特异性。非对称流场-流动分级用于表征具有不同ZnPC与聚合物比例的胶束及其在人血浆中的稳定性。具有最低有效载荷的ZnPC-M(0.2和0.4%ZnPCw/w)在血浆中最稳定,表现出最小的ZnPC转移到脂蛋白,并在三种癌细胞系中诱导最高的光毒性。将对肝细胞生长因子受体(MET)或表皮生长因子受体(EGFR)具有结合特异性的纳米抗体(Nbs)与ZnPC-M缀合以促进细胞靶向和内化。MET和EGFR靶向胶束增强了表达靶受体的细胞中的缔合和光毒性。总之,这些结果表明,用Nbs修饰的ZnPC-M靶向癌细胞上的过表达蛋白可能为目前批准的制剂提供更好的替代方案。
    Photodynamic therapy (PDT) is a suitable alternative to currently employed cancer treatments. However, the hydrophobicity of most photosensitizers (e.g., zinc phthalocyanine (ZnPC)) leads to their aggregation in blood. Moreover, non-specific accumulation in skin and low clearance rate of ZnPC leads to long-lasting skin photosensitization, forcing patients with a short life expectancy to remain indoors. Consequently, the clinical implementation of these photosensitizers is limited. Here, benzyl-poly(ε-caprolactone)-b-poly(ethylene glycol) micelles encapsulating ZnPC (ZnPC-M) were investigated to increase the solubility of ZnPC and its specificity towards cancers cells. Asymmetric flow field-flow fractionation was used to characterize micelles with different ZnPC-to-polymer ratios and their stability in human plasma. The ZnPC-M with the lowest payload (0.2 and 0.4% ZnPC w/w) were the most stable in plasma, exhibiting minimal ZnPC transfer to lipoproteins, and induced the highest phototoxicity in three cancer cell lines. Nanobodies (Nbs) with binding specificity towards hepatocyte growth factor receptor (MET) or epidermal growth factor receptor (EGFR) were conjugated to ZnPC-M to facilitate cell targeting and internalization. MET- and EGFR-targeting micelles enhanced the association and the phototoxicity in cells expressing the target receptor. Altogether, these results indicate that ZnPC-M decorated with Nbs targeting overexpressed proteins on cancer cells may provide a better alternative to currently approved formulations.
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  • 文章类型: Journal Article
    主客体药物递送系统(HGDDS)提供了一种整合生物医学功能的简便方法,包括有效的药物装载,被动瞄准,和控制药物释放。然而,开发具有主动靶向的HGDDS受到流行的大环化合物的难以功能化的阻碍。在这里,我们报道了一种基于生物素修饰的磺化Azocalix[4]芳烃(生物素-SAC4A)的主动靶向HGDDS,可有效地将药物输送到癌细胞中以提高抗肿瘤效果。通过酰胺缩合和偶氮偶合合成了生物素-SAC4A。生物素-SAC4A通过偶氮和生物素基团表现出缺氧响应性靶向和主动靶向,分别。DOX@生物素-SAC4A,通过在生物素-SAC4A中加载阿霉素(DOX)制备,在体外和体内评估肿瘤靶向和治疗。DOX@生物素-SAC4A制剂在体外有效杀死癌细胞,并且比没有主动靶向的类似制剂更有效地将DOX递送至病变。因此,DOX@Biotin-SAC4A显著进步了游离DOX的体内抗肿瘤感化。容易制备的生物素-SAC4A提供强DOX络合,主动靶向,和缺氧触发的释放,为HGDDS中有效的乳腺癌化疗提供了有利的宿主。此外,生物素-SAC4A还具有递送用于其他治疗方式和疾病的药剂的潜力。
    Host-guest drug delivery systems (HGDDSs) provided a facile method for incorporating biomedical functions, including efficient drug-loading, passive targeting, and controlled drug release. However, developing HGDDSs with active targeting is hindered by the difficult functionalization of popular macrocycles. Herein, we report an active targeting HGDDS based on biotin-modified sulfonated azocalix[4]arene (Biotin-SAC4A) to efficiently deliver drug into cancer cells for improving anti-tumor effect. Biotin-SAC4A was synthesized by amide condensation and azo coupling. Biotin-SAC4A demonstrated hypoxia responsive targeting and active targeting through azo and biotin groups, respectively. DOX@Biotin-SAC4A, which was prepared by loading doxorubicin (DOX) in Biotin-SAC4A, was evaluated for tumor targeting and therapy in vitro and in vivo. DOX@Biotin-SAC4A formulation effectively killed cancer cells in vitro and more efficiently delivered DOX to the lesion than the similar formulation without active targeting. Therefore, DOX@Biotin-SAC4A significantly improved the in vivo anti-tumor effect of free DOX. The facilely prepared Biotin-SAC4A offers strong DOX complexation, active targeting, and hypoxia-triggered release, providing a favorable host for effective breast cancer chemotherapy in HGDDSs. Moreover, Biotin-SAC4A also has potential to deliver agents for other therapeutic modalities and diseases.
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  • 文章类型: Journal Article
    纳米材料科学最近的进步为创造可靠的,有效,高度准确,和用户友好的生物医学系统。率先将天然细胞膜整合到复杂的纳米载体结构中,细胞膜伪装已经成为调节药物输送的一种变革性方法,提供最小免疫原性和主动靶向能力的好处。然而,具有这种伪装的纳米材料的效用受到诸如次优靶向精度和治疗效果不佳等挑战的限制。量身定制的细胞膜工程站在生物医学的最前沿,为纳米平台配备进行更复杂操作的能力。这篇综述首先考察了细胞膜工程中流行的方法,聚光灯策略,如直接化学修饰,脂质插入,膜杂交,代谢聚糖标记,和基因工程。在此之后,对各种纳米材料的独特属性进行了评估,提供由尖端工程细胞膜伪装驱动的实质性进步和应用的深入审查。该论述通过概述工程细胞膜伪装在纳米材料应用中的显着影响而达到顶峰,并预测其在变革性医疗技术中的开创性作用。可以设想,本文提供的见解将为工程细胞膜伪装纳米技术的创新和完善提供新的途径。
    Recent strides in nanomaterials science have paved the way for the creation of reliable, effective, highly accurate, and user-friendly biomedical systems. Pioneering the integration of natural cell membranes into sophisticated nanocarrier architectures, cell membrane camouflage has emerged as a transformative approach for regulated drug delivery, offering the benefits of minimal immunogenicity coupled with active targeting capabilities. Nevertheless, the utility of nanomaterials with such camouflage is curtailed by challenges like suboptimal targeting precision and lackluster therapeutic efficacy. Tailored cell membrane engineering stands at the forefront of biomedicine, equipping nanoplatforms with the capacity to conduct more complex operations. This review commences with an examination of prevailing methodologies in cell membrane engineering, spotlighting strategies such as direct chemical modification, lipid insertion, membrane hybridization, metabolic glycan labeling, and genetic engineering. Following this, an evaluation of the unique attributes of various nanomaterials is presented, delivering an in-depth scrutiny of the substantial advancements and applications driven by cutting-edge engineered cell membrane camouflage. The discourse culminates by recapitulating the salient influence of engineered cell membrane camouflage within nanomaterial applications and prognosticates its seminal role in transformative healthcare technologies. It is envisaged that the insights offered herein will catalyze novel avenues for the innovation and refinement of engineered cell membrane camouflaged nanotechnologies.
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  • 文章类型: Journal Article
    细胞屏障是生物活性化合物进入细胞以完成其生物学功能的主要瓶颈。这限制了它们的生物医学应用。纳米载体已经证明了通过克服细胞内屏障的级联来包封生物活性化合物并有效地将其递送到靶细胞中以实现期望的治疗和诊断效果的高潜力和益处。在这次审查中,我们在药物输送和纳米载体之前引入了细胞屏障,以及总结纳米载体增加细胞内化的最新进展和策略,促进细胞内贩运,克服耐药性,靶向亚细胞位置和控制药物释放。最后,讨论了纳米载体用于细胞内药物递送的未来前景,主要关注潜在挑战和未来方向。我们的综述概述了纳米载体的细胞内药物递送,这可能会鼓励纳米载体的未来发展,以有效和精确地将药物递送到广泛的细胞和亚细胞靶标中。
    The cellular barriers are major bottlenecks for bioactive compounds entering into cells to accomplish their biological functions, which limits their biomedical applications. Nanocarriers have demonstrated high potential and benefits for encapsulating bioactive compounds and efficiently delivering them into target cells by overcoming a cascade of intracellular barriers to achieve desirable therapeutic and diagnostic effects. In this review, we introduce the cellular barriers ahead of drug delivery and nanocarriers, as well as summarize recent advances and strategies of nanocarriers for increasing internalization with cells, promoting intracellular trafficking, overcoming drug resistance, targeting subcellular locations and controlled drug release. Lastly, the future perspectives of nanocarriers for intracellular drug delivery are discussed, which mainly focus on potential challenges and future directions. Our review presents an overview of intracellular drug delivery by nanocarriers, which may encourage the future development of nanocarriers for efficient and precision drug delivery into a wide range of cells and subcellular targets.
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