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Mesoporous silica nano-adjuvant triggers pro-inflammatory responses in Caco-2/peripheral blood mononuclear cell (PBMC) co-cultures 介孔二氧化硅纳米佐剂触发Caco-2/外周血单核细胞(PBMC)共培养的促炎反应
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1177/18495435221088374
M. Ghasemi, B. Bakhshi, R. Khashei, S. Soudi
The aim of this study was to evaluate the cytotoxicity and immune-stimulatory effect of Mesoporous silica nanoparticle (MSN) Nano-adjuvant on pro-inflammatory cytokines and pattern recognition receptors (PRR) genes expression in Caco-2/PBMC co-culture model. MSNs were synthesized and characterized by scanning electron microscope (SEM), Brunauer Emmett Teller (BET) and Barrett Joyner Halenda (BJH) techniques. The BET specific surface area of MSNs was around 947 m2/g and the total pore volume and average pore diameter were 1.5 cm3/g and 8.01 nm, respectively. At the concentration of 10 µg/mL, MSN showed a low and time-dependent cytotoxicity on Caco-2 cells, while no cytotoxic effect was observed for 0.1 and 1 µg/mL concentrations after 24, 48 and 72 h. The expression of pro-inflammatory cytokines genes (IL-1, IL-8 and TNF-α) in co-cultures treated with different concentrations of MSN showed a dose-dependent significant increase up to 17.44, 2.722 and 4.34 folds, respectively, while the expression augmentation of IL-1 gene was significantly higher than the others. This indicates slight stimulation of intestinal inflammation. Different concentrations of MSN significantly increased TLR4 and NOD2 expression to 4.14 and 2.14 folds, respectively. NOD1 was not affected significantly. It can be concluded that MSN might increase protective immune responses against antigens as a vaccine adjuvant candidate. It seems that stimulation of TNF-α, IL-1, and IL-8 expression in enterocytes probably transpires through the agonistic activity of MSN for TLRs including TLR4, while NOD2-associated signaling pathways are also involved. This study provides an overall picture of MSN as a novel and potent oral adjuvant for mucosal immunity.
在Caco-2/PBMC共培养模型中,研究介孔二氧化硅纳米颗粒(MSN)纳米佐剂对促炎细胞因子和模式识别受体(PRR)基因表达的细胞毒性和免疫刺激作用。采用扫描电子显微镜(SEM)、Brunauer Emmett Teller (BET)和Barrett Joyner Halenda (BJH)技术对MSNs进行了表征。MSNs的BET比表面积约为947 m2/g,总孔容和平均孔径分别为1.5 cm3/g和8.01 nm。在浓度为10µg/mL时,MSN对Caco-2细胞的细胞毒性较低,且具有时间依赖性,而浓度为0.1和1µg/mL时,24、48和72 h均未观察到细胞毒性作用。不同浓度MSN处理的共培养中,促炎因子基因IL-1、IL-8和TNF-α的表达量呈剂量依赖性显著增加,分别增加了17.44倍、2.722倍和4.34倍,其中IL-1基因的表达量增幅显著高于其他基因。这表明肠道炎症受到轻微刺激。不同浓度的MSN显著提高了TLR4和NOD2的表达量,分别达到4.14倍和2.14倍。NOD1未受明显影响。由此可见,作为疫苗佐剂候选物,MSN可能增强对抗原的保护性免疫应答。似乎对肠细胞中TNF-α、IL-1和IL-8表达的刺激可能是通过MSN对tlr(包括TLR4)的激动作用而发生的,同时也参与了nod2相关的信号通路。本研究提供了MSN作为一种新的有效的粘膜免疫口服佐剂的整体图景。
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引用次数: 2
Gold nanotheranostics: future emblem of cancer nanomedicine. 黄金纳米治疗:癌症纳米医学的未来标志。
Q1 Engineering Pub Date : 2021-10-26 eCollection Date: 2021-01-01 DOI: 10.1177/18495435211053945
Bankuru Navyatha, Seema Nara

Cancer nanotheranostics aims at providing alternative approaches to traditional cancer diagnostics and therapies. In this context, plasmonic nanostructures especially gold nanostructures are intensely explored due to their tunable shape, size and surface plasmon resonance (SPR), better photothermal therapy (PTT) and photodynamic therapy (PDT) ability, effective contrast enhancing ability in Magnetic Resonance imaging (MRI) and Computed Tomography (CT) scan. Despite rapid breakthroughs in gold nanostructures based theranostics of cancer, the translation of gold nanostructures from bench side to human applications is still questionable. The major obstacles that have been facing by nanotheranostics are specific targeting, poor resolution and photoinstability during PTT etc. In this regard, various encouraging studies have been carried out recently to overcome few of these obstacles. Use of gold nanocomposites also overcomes the limitations of gold nanostructure probes and emerged as good nanotheranostic probe. Hence, the present article discusses the advances in gold nanostructures based cancer theranostics and mainly emphasizes on the importance of gold nanocomposites which have been designed to decipher the past questions and limitations of in vivo gold nanotheranostics.

癌症纳米诊断学旨在为传统的癌症诊断和治疗提供替代方法。在这种背景下,等离子体纳米结构特别是金纳米结构由于其可调谐的形状、大小和表面等离子体共振(SPR),更好的光热治疗(PTT)和光动力治疗(PDT)能力,以及在磁共振成像(MRI)和计算机断层扫描(CT)中有效的对比度增强能力而受到人们的广泛关注。尽管基于金纳米结构的癌症治疗取得了快速突破,但将金纳米结构从实验室应用到人类应用仍然存在疑问。纳米治疗面临的主要障碍是特异性靶向、分辨率差和PTT过程中的光不稳定性等。在这方面,最近进行了各种令人鼓舞的研究,以克服这些障碍中的少数几个。金纳米复合材料的使用也克服了金纳米结构探针的局限性,成为一种良好的纳米治疗探针。因此,本文讨论了基于金纳米结构的癌症治疗的进展,并着重强调了金纳米复合材料的重要性,该复合材料被设计用于破解体内金纳米治疗过去的问题和局限性。
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引用次数: 4
Green synthesis of gold nanoparticles using Acai berry and Elderberry extracts and investigation of their effect on prostate and pancreatic cancer cells. 利用巴西莓和接骨木提取物绿色合成金纳米颗粒及其对前列腺和胰腺癌细胞影响的研究。
Q1 Engineering Pub Date : 2021-02-16 eCollection Date: 2021-01-01 DOI: 10.1177/1849543521995310
Nicole Remaliah Samantha Sibuyi, Velaphi Clement Thipe, Kiandokht Panjtan-Amiri, Mervin Meyer, Kattesh V Katti

Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants contain phytochemicals that has been used traditionally for treatment of various diseases, and proved to be non-toxic to healthy tissues. These phytochemicals play an important role in bio-reduction processes as reducing and stabilizing agents, and renders NPs selective toxicity towards diseased tissues. The study reports on the synthesis of AuNPs using Acai berry (AB) and Elderberry (EB) extracts and their anti-cancer properties. Formation of berry-AuNPs was confirmed through measurement of physico-chemical properties. The stability of the AuNPs was tested in biocompatible solutions. Anti-cancer activity of berry extracts and AuNPs was evaluated on the prostate (PC-3) and pancreatic (Panc-1) cancer cells. The berry extracts did not show toxicity to the cells, except for AB extracts on PC-3 cells at higher concentrations. The berry-AuNPs showed potential anti-cancer activities, and these effects could be further exploited for treatment of both the prostate and pancreatic cancers. Further studies are required to study the NP mechanism of action and specificity, as well as identify the phytochemicals involved in the synthesis of AuNPs.

绿色纳米技术因其生态友好和经济的生物合成方案而受到广泛关注。利用植物次生代谢物合成金纳米颗粒(AuNPs)被认为是一种更安全、更便宜的选择。植物含有传统上用于治疗各种疾病的植物化学物质,并被证明对健康组织无毒。这些植物化学物质作为还原剂和稳定剂在生物还原过程中发挥重要作用,并使NPs对病变组织具有选择性毒性。本文报道了巴西莓(Acai berry, AB)和接骨木莓(Elderberry, EB)提取物合成AuNPs及其抗癌作用。通过物理化学性质的测定证实了浆果aunps的形成。在生物相容性溶液中测试了AuNPs的稳定性。研究了浆果提取物和AuNPs对前列腺(PC-3)和胰腺(Panc-1)癌细胞的抗癌作用。除AB提取物在较高浓度下对PC-3细胞有毒性作用外,浆果提取物对细胞无毒性作用。浆果- aunps显示出潜在的抗癌活性,这些作用可以进一步用于前列腺癌和胰腺癌的治疗。需要进一步研究NP的作用机制和特异性,以及鉴定AuNPs合成过程中涉及的植物化学物质。
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引用次数: 30
Effect of intracellular uptake of nanoparticle-encapsulated trehalose on the hemocompatibility of allogeneic valves in the VS83 vitrification protocol. 在 VS83 玻璃化方案中,纳米颗粒包裹的曲哈洛糖的细胞内吸收对异体瓣膜血液相容性的影响。
Q1 Engineering Pub Date : 2020-12-29 eCollection Date: 2020-01-01 DOI: 10.1177/1849543520983173
Balamurugan Vasudevan, Qing Chang, Bin Wang, Siyang Huang, Yulong Sui, Wenjie Zhu, Qing Fan, Yisheng Song

Trehalose is a disaccharide molecule consisting of two molecules of glucose. Industrially, trehalose is derived from corn starch and utilized as a drug. This study aims to examine whether the integration of nanoparticle-encapsulated trehalose to the Ice-Free Cryopreservation (IFC) method for preserving heart valves has better cell viability, benefits to protect the extracellular matrix (ECM), and reduce immune response after storage. For the experiment to be carried out, we obtained materials, and the procedures were carried out in the following manner. The initial step was the preparation of hydroxyapatite nanoparticles, followed by precipitation to acquire Apatite colloidal suspensions. Animals were obtained, and their tissue isolation and grouping were done ethically. All samples were then divided into four groups, Control group, Conventional Frozen Cryopreservation (CFC) group, IFC group, and IFC + T (IFC with the addition of 0.2 M nanoparticle-encapsulated Trehalose) group. Histological analysis was carried out via H&E staining, ECM components were stained with Modified Weigert staining, and the Gomori Ammonia method was used to stain reticular fibers. Alamar Blue assay was utilized to assess cell viability. Hemocompatibility was evaluated, and samples were processed for immunohistochemistry (TNFα and IL-10). Hemocompatibility was quantified using Terminal Complement Complex (TCC) and Neutrophil elastase (NE) as an indicator. The results of the H&E staining revealed less formation of extracellular ice crystals and intracellular vacuoles in the IFC + T group compared with all other groups. The CFC group's cell viability showed better viability than the IFC group, but the highest viability was exhibited in the IFC + T group (70.96 ± 2.53, P < 0.0001, n = 6). In immunohistochemistry, TNFα levels were lowest in both IFC and IFC + T group, and IL-10 expression had significantly reduced in IFC and IFC + T group. The results suggested that the nanoparticle encapsulated trehalose did not show significant hemocompatibility issues on the cryopreserved heart valves.

曲哈糖是一种双糖分子,由两个葡萄糖分子组成。在工业上,曲哈洛糖从玉米淀粉中提取并用作药物。本研究旨在探讨在无冰低温保存(IFC)心脏瓣膜的方法中加入纳米颗粒封装的曲哈洛糖是否能提高细胞存活率、保护细胞外基质(ECM)并减少储存后的免疫反应。为了进行实验,我们获取了材料,并按以下方式进行了操作。第一步是制备羟基磷灰石纳米颗粒,然后沉淀以获得磷灰石胶体悬浮液。获得动物,并对其组织进行伦理分离和分组。然后将所有样本分为四组,即对照组、传统冷冻冷藏(CFC)组、IFC 组和 IFC + T(IFC,添加 0.2 M 纳米粒子包裹的树海糖)组。组织学分析采用 H&E 染色法,ECM 成分采用改良魏格染色法,网状纤维采用 Gomori Ammonia 染色法。阿拉玛蓝检测法用于评估细胞存活率。评估血液相容性,并对样本进行免疫组化处理(TNFα 和 IL-10)。血液相容性以末端补体复合物(TCC)和中性粒细胞弹性蛋白酶(NE)为指标进行量化。H&E 染色结果显示,与其他各组相比,IFC + T 组细胞外冰晶和细胞内空泡的形成较少。CFC 组的细胞存活率高于 IFC 组,但 IFC + T 组的细胞存活率最高(70.96 ± 2.53,P < 0.0001,n = 6)。免疫组化结果显示,IFC 组和 IFC + T 组的 TNFα 水平最低,IFC 组和 IFC + T 组的 IL-10 表达明显降低。结果表明,纳米颗粒包裹的曲哈洛糖对冷冻保存的心脏瓣膜没有明显的血液相容性问题。
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引用次数: 0
Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials. CRISPR/Cas9 在乳腺癌中的治疗应用以及金纳米材料的输送潜力。
Q1 Engineering Pub Date : 2020-12-24 eCollection Date: 2020-01-01 DOI: 10.1177/1849543520983196
Jananee Padayachee, Moganavelli Singh

Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.

在全球范围内,大约每 4 名女性癌症患者中就有 1 人被诊断为乳腺癌(BC)。尽管乳腺癌的诊断和治疗取得了重大进展,但许多患者仍会出现转移或复发。因此,需要能够选择性地有效杀死恶性细胞的新型治疗策略。直接针对 BC 发展过程中出现的遗传和表观遗传畸变是一种很有前景的策略,可以克服目前针对肿瘤表型的疗法的局限性。簇状规则间距短回文重复序列(CRISPR)/Cas系统仅由一个与Cas9核酸酶结合的易于修改的单导RNA(sgRNA)序列组成,与早期的系统相比,它的简便性和高效性彻底改变了基因组编辑。CRISPR/Cas9 及其相关的催化失活 dCas9 变体有助于敲除过表达基因、校正失活基因中的突变以及重编程表观遗传景观以损害 BC 的生长。要在体内实现高效的基因组编辑,需要一种载体来将元件输送到靶细胞。金纳米材料,包括金纳米颗粒和纳米团簇,显示出许多有利的特性,促进了它们在治疗学、输送载体、成像和光热剂方面的广泛应用。本综述重点介绍了 CRISPR/Cas9 在治疗 BCs 方面的治疗应用,并简要介绍了金纳米材料及其在 CRISPR/Cas9 传输方面的潜力。
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引用次数: 0
Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury. 纳米治疗对急性脑损伤中兴奋毒性和氧化应激的调节。
Q1 Engineering Pub Date : 2020-11-04 eCollection Date: 2020-01-01 DOI: 10.1177/1849543520970819
Rick Liao, Thomas R Wood, Elizabeth Nance

Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood-brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia-ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.

兴奋性毒性是发生在中风、创伤性脑损伤(TBI)和全脑缺血(如围产期窒息)时的主要病理过程。兴奋性毒性是由突触内兴奋性神经递质过多引发的,引起钠和钙流入过多的有害级联反应,产生活性氧,线粒体损伤,最终导致细胞死亡。有多个潜在的干预点来对抗兴奋毒性和下游氧化应激,但目前还没有临床批准的治疗方法用于这一特定目的。为了使治疗药物对兴奋性毒性有效,治疗药物必须在适当的时间以适当的浓度积聚在疾病部位。纳米技术可以为治疗递送提供益处,包括克服血脑屏障等生理障碍,保护货物免于降解,以及提供药物的可控释放。这篇综述评估了纳米疗法在脑卒中、脑外伤和缺氧缺血中对抗兴奋性毒性的应用,重点是减轻氧化应激,并考虑了临床转化的途径。
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引用次数: 10
NanoBioMedicine 纳米生物医学
Q1 Engineering Pub Date : 2020-01-01 DOI: 10.1007/978-981-32-9898-9
S. Saxena, S. Khurana, Nanobiomedicine
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引用次数: 11
Preclinical verification of the efficacy by targeting peptide-linked liposomal nanoparticles for hepatocellular carcinoma therapy. 靶向肽链脂质体纳米颗粒治疗肝癌疗效的临床前验证。
Q1 Engineering Pub Date : 2019-12-30 eCollection Date: 2019-01-01 DOI: 10.1177/1849543519880762
Cheng-Der Wu, Jen-Chieh Lee, Hang-Chung Wu, Chung-Wei Lee, Chih-Feng Lin, Ming-Chen Hsu, Chin-Tarng Lin

The purpose of this study was to investigate the efficacy of targeting peptides chemotherapy to overcome adverse event in the conventional chemotherapy for human hepatocellular carcinoma. Previously we reported several cancer-targeting peptides that bind specifically to cancer cells and their vascular endothelia: L-peptide (anti-cancer cell membrane), RLLDTNRPLLPY; SP-94-peptide (anti-hepatoma cell membrane), SFSHHTPILP; PC5-52-peptide (anti-tumor endothelia), SVSVGMKPSPRP; and control peptide, RLLDTNRGGGGG. In this study, these peptides were linked to liposomal iron oxide nanoparticles to localize the targeted tumor cells and endothelia, and to dextran-coated liposomal doxorubicin (L-D) to treat nonobese diabetic severe combined immunodeficient mice bearing hepatoma xenografts. Our results showed that L-peptide-linked liposomal doxorubicin could inhibit tumor growth with very mild adverse events. Use of the control peptide led to a decrease in the xenograft size but also led to marked apoptotic change in the visceral organ. In conclusion, L-peptide-linked liposomal doxorubicin, SP-94-peptide, and PC5-52-peptide can be used for the treatment of hepatoma xenografts in nonobese diabetic severe combined immunodeficient mice with minimal adverse events.

本研究的目的是探讨靶向肽化疗对人肝癌常规化疗中不良事件的影响。之前我们报道了几种与癌细胞及其血管内皮特异性结合的癌症靶向肽:l -肽(抗癌细胞膜),RLLDTNRPLLPY;sp -94肽(抗肝癌细胞膜),SFSHHTPILP;pc5 -52肽(抗肿瘤内皮素);和控制肽RLLDTNRGGGGG。在这项研究中,这些肽与脂质体氧化铁纳米颗粒结合,以定位目标肿瘤细胞和内皮,并与葡聚糖包被的脂质体阿霉素(L-D)结合,治疗非肥胖糖尿病严重联合免疫缺陷小鼠肝癌移植。我们的研究结果表明,l肽连接的脂质体阿霉素可以抑制肿瘤生长,并且不良反应非常轻微。对照肽的使用导致异种移植物大小的减少,但也导致内脏器官中明显的凋亡变化。综上所述,l肽连接脂质体阿霉素、sp -94肽和pc5 -52肽可用于治疗非肥胖糖尿病严重联合免疫缺陷小鼠的肝癌异种移植,且不良事件最小。
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引用次数: 6
HIV: Biology to Treatment 艾滋病病毒:从生物学到治疗
Q1 Engineering Pub Date : 2019-09-25 DOI: 10.1007/978-981-32-9898-9_7
A. S. Verma, Vipin Kumar, M. Saha, S. Dutta, Anchal Singh
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引用次数: 4
Diagnosis of Tuberculosis: Nanodiagnostics Approaches 结核的诊断:纳米诊断方法
Q1 Engineering Pub Date : 2019-09-25 DOI: 10.1007/978-981-32-9898-9_11
A. Gupta, Amit Singh, Sarman Singh
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引用次数: 6
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