BACKGROUND & AIMS: BACKGROUND:Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. METHODS:CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). RESULTS:CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. CONCLUSIONS:Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor.

背景与目标：

BACKGROUND & AIMS: :One of the major challenges for new therapeutics molecules to enter the clinic remains improving their bioavailability and cellular uptake. Therefore, delivery has become a key stone in therapeutic development and several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs) or protein transduction domain (PTD). PTDs or CPPs were discovered twenty years ago, based on the potency of several proteins to enter cells and nowadays, numerous peptide carriers have been described and successfully applied for ex vivo and in vivo delivery of varying therapeutic molecules. Two CPP-strategies have been reported; the first one requires chemical linkage between the drug and the carrier for cellular drug internalization and the second is based on the formation of stable complexes with drugs depending on their chemical nature. Peptide-Based-Nanoparticle Devices (PBND), correspond to short amphipathic peptides able to form stable nanoparticles with proteins and/or nucleic acids. Three PBND-families, PEP, MPG and CADY have been described, these carriers mainly enter cells independently of the endosomal pathway and efficiently deliver cargoes in a large variety of challenging cell lines as well as in animal models. This review will focus on the structure/function relationship of the PBND: CADY, PEP and MPG, in the general context of drug delivery. It will also highlight the requirement of primary or secondary amphipathic carriers for in vitro and in vivo delivery of therapeutic molecules and provide an update of their pre-clinical evaluation.

背景与目标： : 新的治疗分子进入临床的主要挑战之一仍然是提高其生物利用度和细胞摄取。因此，递送已成为治疗发展的关键石，并且已经设计了几种技术来改善治疗分子的细胞摄取，包括细胞穿透肽 (CPPs) 或蛋白质转导结构域 (PTD)。PTDs或cpp是在20年前发现的，基于几种蛋白质进入细胞的能力，如今，已经描述了许多肽载体，并成功地用于各种治疗分子的体外和体内递送。已经报道了两种CPP策略; 第一种需要药物与载体之间的化学连接以进行细胞药物内在化，第二种是基于药物的化学性质与药物形成稳定的复合物。基于肽的纳米颗粒装置 (PBND) 对应于能够与蛋白质和/或核酸形成稳定纳米颗粒的短两亲肽。已经描述了三个PBND家族，PEP，MPG和CADY，这些载体主要独立于内体途径进入细胞，并在各种具有挑战性的细胞系以及动物模型中有效地输送货物。这篇综述将集中在药物递送的一般背景下，PBND: CADY，PEP和MPG的结构/功能关系。它还将强调一级或二级两亲性载体在体外和体内递送治疗分子的需求，并提供其临床前评估的更新。

BACKGROUND & AIMS: :We studied the effectiveness of trilysine (Lys3), tetralysine (Lys4), pentalysine (Lys5), and poly-l-lysine (PLL) (MW 50000) on lambda-DNA nanoparticle formation and characterized the size, shape, and stability of nanoparticles. Light scattering experiments showed EC50 (lysine concentration at 50% DNA compaction) values of approximately 0.0036, 2, and 20 micromol/L, respectively, for PLL, Lys5, and Lys4 at 10 mM [Na+]. Plots of log EC50 versus log [Na+] showed positive slopes of 1.09 and 1.7, respectively, for Lys4 and Lys5 and a negative slope of -0.1 for PLL. Hydrodynamic radii of oligolysine condensed particles increased (48-173 nm) with increasing [Na+], whereas no significant change occurred to nanoparticles formed with PLL. There was an increase in the size of nanoparticles formed with Lys5 at >40 degrees C, whereas no such change occurred with PLL. The DNA melting temperature increased with oligolysine concentration. These results indicate distinct differences in the mechanism(s) by which oligolysines and PLL provoke DNA condensation to nanoparticles.

背景与目标： : 我们研究了三赖氨酸 (Lys3)，四赖氨酸 (Lys4)，五赖氨酸 (Lys5) 和聚-l-赖氨酸 (PLL) (MW 50000) 对lambda-DNA纳米颗粒形成的有效性，并表征了纳米颗粒的大小，形状和稳定性。光散射实验显示，对于PLL，Lys5和Lys4在10 mM [Na +] 下的EC50 (50% DNA压实时的赖氨酸浓度) 值分别约为0.0036、2和20微摩尔/L。log EC50与log [Na] 的图分别显示Lys4和Lys5的正斜率为1.09和1.7，PLL的负斜率为-0.1。低聚赖氨酸缩合颗粒的流体力学半径随着 [Na] 的增加而增加 (48-173 nm)，而PLL形成的纳米颗粒没有显着变化。在> 40摄氏度下，用Lys5形成的纳米颗粒的尺寸增加，而PLL没有发生这种变化。DNA熔化温度随低聚赖氨酸浓度的增加而增加。这些结果表明低聚物和PLL引发DNA缩合到纳米颗粒的机理存在明显差异。

BACKGROUND & AIMS: :Cerium oxide nanoparticles (CNPs) as an antioxidant have been used frequently to attenuate hyperglycaemia oxidative damage in different organs. We investigated the impact CNPs on the qualitative and quantitative sperm parameters, spermatogenesis and NFE2-related factor 2 (Nrf2) expression as a major contributor of antioxidant defence in the male diabetic rats. Twenty-four male rats were divided into four groups. Controls received only mouse food and water. Second group were treated with CNPs (30 mg kg-1  day-1 ) for 2 weeks. Rats in third group received streptozotocin (STZ) (60 mg/kg). In fourth group, animals became diabetic and received CNPs (30 mg kg-1  day-1 ) for 2 weeks. The results showed a significant abnormality in the sperm parameters and histopathological patterns of testes in the diabetic group compared to the control group and CNPs treatment significantly improved all testicular parameters. Following CNPs administration, sperm DNA fragmentation significantly reduced in the STZ-treated rats. Moreover, after CNPs intake in the STZ-treated rats, Nfr2 expression levels increased significantly. Overall, CNPs administration on the diabetic rates can attenuate detrimental effects of diabetes on the sperm potential fertility, sperm parameters, DNA integrity and Nrf2 expression levels. This study gives a future prospect to determine the role of CNPs in the context of diabetes.

背景与目标： 氧化铈纳米颗粒 (CNPs) 作为一种抗氧化剂，经常用于减轻不同器官的高血糖氧化损伤。我们研究了CNPs对定性和定量精子参数，精子发生和NFE2-related因子2 (Nrf2) 表达的影响，这是雄性糖尿病大鼠抗氧化防御的主要贡献者。将24只雄性大鼠分为四组。对照组只收到老鼠的食物和水。第二组用CNPs (30 mg kg-1天-1) 治疗2周。第三组大鼠接受链脲佐菌素 (STZ) (60 mg/kg)。在第四组中，动物成为糖尿病患者并接受CNPs (30 mg kg-1天-1) 治疗2周。结果显示，与对照组相比，糖尿病组的精子参数和睾丸的组织病理学模式明显异常，CNPs治疗显着改善了所有睾丸参数。施用CNPs后，STZ处理的大鼠的精子DNA断裂显着减少。此外，在STZ处理的大鼠中摄入CNPs后，Nfr2表达水平显着增加。总体而言，CNPs给药对糖尿病的影响可以减轻糖尿病对精子的潜在生育力，精子参数，DNA完整性和Nrf2表达水平的不利影响。这项研究为确定CNPs在糖尿病中的作用提供了未来的前景。

BACKGROUND & AIMS: :Despite great advances in the fight against cancer, traditional chemotherapy has been hindered by the dose dependent adverse side effects that reduce the usable doses for effective therapy. This has been associated to drug resistance in tumor cells that often cause relapse and therapy failure. These drawbacks have been tackled by combining different therapeutic regiments that prevent drug resistance while decreasing the chemotherapy dose required for efficacious ablation of cancer. In fact, new metallic compounds have been in a continuous development to extend the existing chemotherapy arsenal for these combined regimens. Here, we demonstrate that combination of a metallic compound (TS265), previously characterized by our group, with photothermy circumvents cells resistant to Doxorubicin (DOX). We first engendered a colorectal carcinoma cell line (HCT116) highly resistant to DOX, whose viability was diminished after administration of TS265. Cancer cell death was potentiated by challenging these cells with 14 nm spherical gold nanoparticles followed by laser irradiation at 532 nm. The combination of TS265 with photothermy lead to 65% cell death of the DOX resistant cells without impacting healthy cells. These results support the use of combined chemotherapy and photothermy in the visible spectrum as an efficient tool for drug resistant tumors.

背景与目标： : 尽管在对抗癌症方面取得了巨大进步，但传统的化学疗法受到剂量依赖性不良副作用的阻碍，这些副作用减少了有效治疗的可用剂量。这与经常导致复发和治疗失败的肿瘤细胞的耐药性有关。通过结合不同的治疗方案来解决这些缺点，这些方案可防止耐药性，同时减少有效消融癌症所需的化学疗法剂量。实际上，新的金属化合物一直在不断发展，以扩展这些联合疗法的现有化疗武器库。在这里，我们证明了先前由我们小组表征的金属化合物 (TS265) 与光热的结合，可以避免对阿霉素 (DOX) 具有抗性的细胞。我们首先产生了对DOX具有高度抗性的大肠癌细胞系 (HCT116)，该细胞系在施用ts265后活力降低。通过用14 nm球形金纳米颗粒挑战这些细胞，然后在532  nm处进行激光照射，可以增强癌细胞的死亡。TS265与光热的组合导致DOX抗性细胞的65% 细胞死亡，而不影响健康细胞。这些结果支持在可见光谱中使用联合化疗和照相疗法作为耐药肿瘤的有效工具。

BACKGROUND & AIMS: :Abundant desmoplastic stroma, which typically exists in pancreatic ductal adenocarcinoma (PDAC), can act as a natural protective physical barrier rendering insufficient drug delivery and penetration. To address this issue, we herein report a two-step sequential delivery strategy for enhanced pancreatic cancer therapy. In this sequential strategy, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) loaded liposomes (Lip-SNAP) were firstly delivered to pancreatic stellate cells (PSCs) in tumor tissue to inhibit the production of dense stroma, by inhibiting the expression of TGF-β1 and its downstream profibrotic signal transduction. Therefore, the PSC-mediated desmoplastic reaction could be suppressed by inhibiting the expression of fibronectin, α-SMA and collagen. The gemcitabine (GEM) loaded liposomes (Lip-GEM) were administrated subsequently. The enhanced intratumoral penetration of Lip-GEM was then achieved due to the stromal disruption in consequence of NO treatment, thus significantly improving the drug delivery efficiency. The tumor growth inhibition of the two-step sequential delivery of Lip-SNAP and Lip-GEM was investigated on both subcutaneous and orthotopic tumor mouse models, to show the remarkably improved therapeutic efficacy of GEM. Such NO-induced stromal depletion provides a general strategy to overcome the blockage of desmoplastic stroma on other therapeutic agents.

背景与目标： : 通常存在于胰腺导管腺癌 (PDAC) 中的丰富的促结缔组织间质可以作为天然的保护性物理屏障，从而导致药物输送和渗透不足。为了解决这个问题，我们在此报告了用于增强胰腺癌治疗的两步顺序递送策略。在这种顺序策略中，首先将一氧化氮 (NO) 供体S-亚硝基-N-乙酰青霉胺 (SNAP) 脂质体 (Lip-SNAP) 递送到肿瘤组织中的胰腺星状细胞 (psc)，以抑制致密基质的产生，通过抑制TGF-β1的表达及其下游纤维化前信号转导。因此，可以通过抑制纤连蛋白，α-SMA和胶原蛋白的表达来抑制PSC介导的促纤维增生反应。随后给药吉西他滨 (GEM) 负载的脂质体 (Lip-GEM)。随后，由于不进行治疗而导致基质破坏，从而增强了Lip-GEM的瘤内渗透，从而显着提高了药物输送效率。在皮下和原位肿瘤小鼠模型上研究了Lip-SNAP和Lip-GEM两步顺序递送的肿瘤生长抑制作用，以显示GEM的治疗效果显着提高。这种NO诱导的基质耗竭提供了一种通用策略，可以克服其他治疗剂对促增生性基质的阻塞。

BACKGROUND & AIMS: :We have previously introduced the use of the biomaterial chitosan to form chitosan/siRNA nanoparticles for gene silencing protocols. This present study shows that the physicochemical properties (size, zeta potential, morphology and complex stability) and in vitro gene silencing of chitosan/siRNA nanoparticles are strongly dependent on chitosan molecular weight (Mw) and degree of deacetylation (DD). High Mw and DD chitosan resulted in the formation of discrete stable nanoparticles approximately 200 nm in size. Chitosan/siRNA formulations (N:P 50) prepared with low Mw (approximately 10 kDa) showed almost no knockdown of endogenous enhanced green fluorescent protein (EGFP) in H1299 human lung carcinoma cells, whereas those prepared from higher Mw (64.8-170 kDa) and DD (approximately 80%) showed greater gene silencing ranging between 45% and 65%. The highest gene silencing efficiency (80%) was achieved using chitosan/siRNA nanoparticles at N:P 150 using higher Mw (114 and 170 kDa) and DD (84%) that correlated with formation of stable nanoparticles of approximately 200 nm. In conclusion, this work confirms the application of chitosan as a non-viral carrier for siRNA and the importance of polymeric properties for the optimisation of gene silencing using chitosan/siRNA nanoparticles.

背景与目标： : 我们之前已经介绍了使用生物材料壳聚糖形成壳聚糖/siRNA纳米颗粒的基因沉默方案。本研究表明，壳聚糖/siRNA纳米颗粒的理化性质 (大小，zeta电位，形态和复合物稳定性) 和体外基因沉默强烈依赖于壳聚糖分子量 (Mw) 和脱乙酰度 (DD)。高Mw和DD壳聚糖导致形成尺寸约200 nm的离散稳定纳米颗粒。低Mw (约10 kDa) 制备的壳聚糖/siRNA制剂 (N:P 50) 在H1299人肺癌细胞中几乎没有内源性增强绿色荧光蛋白 (EGFP) 的敲除，而由较高Mw (64.8-170 kDa) 和DD (约80%) 制备的那些显示出45% 和65% 之间更大的基因沉默。使用与形成约200纳米的稳定纳米颗粒相关的较高Mw (114和170 kDa) 和DD (84%)，在N:P 150使用壳聚糖/siRNA纳米颗粒获得最高的基因沉默效率 (80%)。总之，这项工作证实了壳聚糖作为siRNA的非病毒载体的应用，以及聚合物特性对于使用壳聚糖/siRNA纳米颗粒优化基因沉默的重要性。

BACKGROUND & AIMS: :The rapid, specific and sensitive detection of nucleic acids is of utmost importance for the identification of infectious agents, diagnosis and treatment of genetic diseases, and the detection of pathogens related to human health and safety. Here we report the development of a simple and sensitive nucleic acid sequence-based and Ru(bpy)3 (2+)-doped silica nanoparticle-labeled lateral flow assay which achieves low limit of detection by using fluorescencent nanoparticles. The detection of the synthetic nucleic acid sequences representative of Trypanosoma mRNA, the causative agent for African sleeping sickness, was utilized to demonstrate this assay. The 30 nm spherical Ru(bpy)3 (2+)-doped silica nanoparticles were prepared in aqueous medium by a novel method recently reported. The nanoparticles were modified by 3-glycidoxypropyl trimethoxysilane in order to conjugate to amine-capped oligonucleotide reporter probes. The fluorescent intensities of the fluorescent assays were quantified on a mictrotiter plate reader using a custom holder. The experimental results showed that the lateral flow fluorescent assay developed was more sensitive compared with the traditional colloidal gold test strips. The limit of detection for the fluorescent lateral flow assay developed is approximately 0.066 fmols as compared to approximately 15 fmols for the colloidal gold. The limit of detection can further be reduced about one order of magnitude when "dipstick" format was used.

背景与目标： : 核酸的快速，特异性和灵敏检测对于鉴定感染原，遗传疾病的诊断和治疗以及与人类健康和安全有关的病原体的检测至关重要。在这里，我们报告了一种简单而灵敏的基于核酸序列和Ru(bpy)3 (2) 掺杂的二氧化硅纳米颗粒标记的侧向流动测定法的开发，该测定法通过使用荧光纳米颗粒实现了低检测限。利用代表锥虫mRNA (非洲昏睡病的病原体) 的合成核酸序列的检测来证明该测定。通过最近报道的一种新方法，在水性介质中制备了30 nm球形Ru(bpy)3 (2) 掺杂的二氧化硅纳米颗粒。纳米颗粒被3-缩水甘油氧基丙基三甲氧基硅烷修饰，以缀合到胺封端的寡核苷酸报告探针。使用定制支架在mictrotiter板读取器上定量荧光测定的荧光强度。实验结果表明，与传统的胶体金试纸相比，开发的侧向流荧光测定法更灵敏。所开发的荧光侧向流测定法的检出限为约0.066 fmols，而胶体金的检出限为约15 fmols。当使用 “量油尺” 格式时，检测极限可以进一步降低约一个数量级。

BACKGROUND & AIMS: :Silver nanoparticles (AgNPS) are an important model system for studying potential environmental risks posed by the use of nanomaterials. So far there is no consensus as to whether toxicity is due to AgNPs themselves or Ag(+) ions leaching from their surfaces. In sea urchin Paracentrotus lividus, AgNPs cause dose dependent developmental defects such as delayed development, bodily asymmetry and shortened or irregular arms, as well as behavioural changes, particularly in swimming patterns, at concentration ∼0.3 mg/L AgNPs. It has been observed that AgNPs are more toxic than their equivalent Ag(+) ion dose.

背景与目标： : 银纳米颗粒 (AgNPS) 是研究纳米材料使用带来的潜在环境风险的重要模型系统。到目前为止，关于毒性是由于AgNPs本身还是Ag () 离子从其表面浸出所致，尚无共识。在海胆副牛鱼中，AgNPs会导致剂量依赖性发育缺陷，例如发育延迟、身体不对称和手臂缩短或不规则，以及行为变化，特别是在游泳模式中，浓度为0.3毫克/升AgNPs。已经观察到AgNPs比其等效的Ag () 离子剂量更具毒性。

BACKGROUND & AIMS: :The increasing use of nano-sized materials in our environment, and in many consumer products, dictates new safety concerns. In particular, adequate experimental models are needed to evaluate skin toxicity of metal oxide ions, commonly found in cosmetic and dermatologic preparations. We have addressed the biological effects of topically applied copper oxide (CuO) nanoparticles in human skin organ cultures, using light and electron microscopy, and biochemical tests. Nanoparticles were more toxic than micro-sized particles, and their effects were stronger when supplied in growth medium than in topical application. Still topically applied CuO nanoparticles induced inflammatory cytokine secretion and necrosis, especially in epidermis deprived of its protective cornea. Since nanoparticle penetration was not seen, we propose that they may adhere to skin surface, react with the local acidic environment, and generate soluble ions that make their way to inner sites. This work illustrates the abilities of skin organ culture to evaluate the biological effects of topically-applied materials on skin in vitro.

背景与目标： : 纳米材料在我们的环境和许多消费产品中越来越多地使用，这引起了新的安全问题。特别是，需要足够的实验模型来评估金属氧化物离子的皮肤毒性，通常在化妆品和皮肤病学制剂中发现。我们已经使用光学和电子显微镜以及生化测试解决了局部应用的氧化铜 (CuO) 纳米颗粒在人体皮肤器官培养物中的生物学作用。纳米颗粒比微型颗粒更具毒性，并且在生长培养基中提供时，其作用比在局部应用中更强。仍局部应用的CuO纳米颗粒可诱导炎性细胞因子分泌和坏死，尤其是在缺乏保护性角膜的表皮中。由于未看到纳米颗粒的渗透，我们建议它们可能粘附在皮肤表面，与局部酸性环境反应，并产生可溶离子，从而进入内部位置。这项工作说明了皮肤器官培养物评估体外局部应用材料对皮肤的生物学作用的能力。

BACKGROUND & AIMS: :In view of minimally-invasive clinical interventions, laser tissue soldering assisted by plasmonic nanoparticles is emerging as an appealing concept in surgical medicine, holding the promise of surgeries without sutures. Rigorous monitoring of the plasmonically-heated solder and the underlying tissue is crucial for optimizing the soldering bonding strength and minimizing the photothermal damage. To this end, we propose a non-invasive, non-contact, and non-ionizing modality for monitoring nanoparticle-assisted laser-tissue interaction and visualizing the localized photothermal damage, by taking advantage of the unique sensitivity of terahertz radiation to the hydration level of biological tissue. We demonstrate that terahertz radiation can be employed as a versatile tool to reveal the thermally-affected evolution in tissue, and to quantitatively characterize the photothermal damage induced by nanoparticle-assisted laser tissue soldering in three dimensions. Our approach can be easily extended and applied across a broad range of clinical applications involving laser-tissue interaction, such as laser ablation and photothermal therapies.

背景与目标： : 鉴于微创的临床干预措施，由等离子体纳米粒子辅助的激光组织焊接正在成为外科医学中一个吸引人的概念，具有无缝线手术的希望。对等离子体加热的焊料和下面的组织进行严格的监控对于优化焊接强度和最大程度地减少光热损伤至关重要。为此，我们提出了一种非侵入性，非接触和非电离方式，用于监测纳米颗粒辅助的激光与组织的相互作用，并通过利用太赫兹辐射对生物组织水合水平的独特敏感性来可视化局部光热损伤。我们证明，太赫兹辐射可以用作一种通用工具，以揭示组织中热影响的演化，并定量表征由纳米颗粒辅助的激光组织焊接在三个维度上引起的光热损伤。我们的方法可以轻松地扩展并应用于涉及激光-组织相互作用的广泛临床应用，例如激光消融和光热疗法。

BACKGROUND & AIMS: :Polyethylene glycol (PEG) has long been used in nanoparticle-based drug or vaccine delivery platforms. In this study, nano-nicotine vaccines (NanoNicVac) were PEGylated to different degrees to investigate the impact of PEG on the immunological efficacy of the vaccine. Hybrid nanoparticles with various degrees of PEGylation (2.5%-30%) were assembled. It was found that 30% PEGylation resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles by dendritic cells. However, increasing the quantity of the PEG could effectively reduce nanoparticle aggregation during storage and improve the stability of the hybrid nanoparticles. Subsequently, nicotine vaccines were synthesized by conjugating nicotine haptens to the differently PEGylated hybrid nanoparticles. In both in vitro and in vivo studies, it was found that a nicotine vaccine with 20% PEGylation (NanoNicVac 20.0) was significantly more stable than the vaccines with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly higher anti-nicotine antibody titer of 3.7 ± 0.6 × 104 in mice than the other NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic study, the lowest brain nicotine concentration of 34 ± 11 ng/g was detected in mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse events were observed in mice immunized with NanoNicVac. In summary, 20% PEGylation confers NanoNicVac with desirable safety, the highest stability, and the best immunological efficacy in mice.

背景与目标： : 聚乙二醇 (PEG) 长期以来一直用于基于纳米颗粒的药物或疫苗递送平台。在这项研究中，纳米尼古丁疫苗 (NanoNicVac) 被不同程度的聚乙二醇化，以研究PEG对疫苗免疫功效的影响。组装具有不同程度的聚乙二醇化 (2.5%-30%) 的杂化纳米颗粒。发现30% 聚乙二醇化导致核-壳结构受损的杂化纳米颗粒。较高浓度的PEG也导致树突状细胞对杂种纳米颗粒的吸收较慢。然而，增加PEG的数量可以有效地减少存储过程中纳米颗粒的聚集，并提高杂化纳米颗粒的稳定性。随后，通过将尼古丁半抗原与不同聚乙二醇化的杂化纳米颗粒结合来合成尼古丁疫苗。在体外和体内研究中，发现具有20% 聚乙二醇化的尼古丁疫苗 (NanoNicVac 20.0) 明显比具有较低聚乙二醇化的疫苗更稳定。此外，与其他浓度较低的PEG的纳米疫苗相比，纳米疫苗20.0在小鼠中诱导出3.7   ±   0.6  ×   104的抗尼古丁抗体滴度显着更高。在随后的药代动力学研究中，在用NanoNicVac 20.0免疫的小鼠中检测到最低脑尼古丁浓度为34  ±   11  ng/g。此外，在用NanoNicVac免疫的小鼠中未观察到明显的不良事件。总之，20% 聚乙二醇化赋予纳米尼伐克在小鼠中具有理想的安全性、最高的稳定性和最佳的免疫功效。

BACKGROUND & AIMS: :Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ± 2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs(+ζ)), negatively (Ag-CALNNS NPs(-2ζ)), and more negatively charged NPs (Ag-CALNNE NPs(-4ζ)), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as a model molecule to create positive, neutral, and negative charges on the surface of the NPs at pH 4-10. We have studied their charge-dependent transport into early developing (cleavage-stage) zebrafish embryos and their effects on embryonic development using dark-field optical microscopy and spectroscopy (DFOMS). We found that all three Ag-peptide NPs passively diffused into the embryos via their chorionic pore canals, and stayed inside the embryos throughout their entire development (120 h), showing charge-independent diffusion modes and charge-dependent diffusion coefficients. Notably, the NPs create charge-dependent toxic effects on embryonic development, showing that the Ag-CALNNK NPs(+ζ) (positively charged) are the most biocompatible while the Ag-CALNNE NPs(-4ζ) (more negatively charged) are the most toxic. By comparing with our previous studies of the same sized citrated Ag and Au NPs, the Ag-peptide NPs are much more biocompatible than the citrated Ag NPs, and nearly as biocompatible as the Au NPs, showing the dependence of nanotoxicity upon the surface charges, surface functional groups, and chemical compositions of the NPs. This study also demonstrates powerful applications of single NP plasmonic spectroscopy for quantitative analysis of single NPs in vivo and in tissues, and reveals the possibility of rational design of biocompatible NPs.

背景与目标： : 纳米材料具有异常高的表面积与体积比和表面确定的理化性质。为了合理设计用于多种应用的生物相容性纳米材料，必须了解它们的表面依赖性毒性。在这项研究中，我们用三种生物相容性肽 (CALNNK，CALNNS，直径为11.7 ± 2.7 nm) 对银纳米颗粒的表面进行了功能化。CALNNE) 分别制备正 (Ag-CALNNK NPs (ζ))，负 (Ag-CALNNS NPs(-2 ζ)) 和更多带负电荷的NPs (Ag-CALNNK NPs(-4 ζ))。每个肽在其C末端的单个氨基酸不同，这使肽序列的影响最小化，并作为模型分子在pH 4-10的NPs表面上产生正电荷，中性电荷和负电荷。我们使用暗场光学显微镜和光谱学 (DFOMS) 研究了它们向早期发育 (卵裂阶段) 斑马鱼胚胎的电荷依赖性转运及其对胚胎发育的影响。我们发现，所有三个Ag肽np都通过其绒毛膜孔管被动扩散到胚胎中，并在整个发育过程中 (120 h) 停留在胚胎内部，显示出与电荷无关的扩散模式和与电荷有关的扩散系数。值得注意的是，NPs对胚胎发育产生电荷依赖性的毒性作用，表明Ag-CALNNK NPs (ζ) (带正电) 是最具生物相容性的，而Ag-CALNNE NPs(-4ζ) (带负电) 是最有毒的。通过与我们先前对相同大小的柠檬酸Ag和Au NPs的研究进行比较，Ag肽NPs比柠檬酸Ag NPs具有更高的生物相容性，并且几乎与Au NPs具有相同的生物相容性，表明纳米毒性对表面电荷，表面官能团，以及NPs的化学成分。这项研究还证明了单个NP等离子体光谱法在体内和组织中定量分析单个NP的强大应用，并揭示了合理设计生物相容性NP的可能性。

BACKGROUND & AIMS: :The findings of a new study by Mohammed et al. show that after repeated hourly or daily topical applications typically used for sunscreens, zinc oxide nanoparticles do not penetrate into the viable epidermis or cause toxicity in human skin. This important study confirms that the known benefits of using zinc oxide nanoparticles in sunscreen clearly outweigh the perceived risks of using nanosunscreens.

背景与目标： 穆罕默德等人的一项新研究的结果表明，通常用于防晒霜的每小时或每天重复局部应用后，氧化锌纳米颗粒不会渗透到活的表皮中或在人体皮肤中引起毒性。这项重要的研究证实，在防晒霜中使用氧化锌纳米颗粒的已知好处显然超过了使用纳米屏幕的感知风险。

BACKGROUND & AIMS: :Banana, citrus and potato peels were subjected to treatment with hydroxyapatite nanoparticle (NP) supplemented purified pectate lyase (NP-PL), isolated from Bacillus megaterium AK2 to produce reducing sugar (RS). At both 50 and 90°C production of RS by NP-PL was almost twofold greater than that by untreated pectate lyase (PL) from each of the three peels. The optimal production of RS from banana and citrus peels were after 24 and 6h of incubation while it was 24 and 4h for potato peels at 50 and 90°C, respectively, on NP-PL treatment. NP-PL could degum raw, decorticated ramie fibers as well as enhance fiber tenacity and fineness. The weight loss of the fibers were 24% and 31% better (compared to PL treatment) after 24 and 48 h of processing. These findings have potential implications for the bio-ethanol, bio-fuel and textile industries.

背景与目标： : 香蕉，柑橘和马铃薯皮用羟基磷灰石纳米颗粒 (NP) 补充的纯化果胶酸裂解酶 (NP-PL) 处理，从巨大芽孢杆菌AK2中分离出来以产生还原糖 (RS)。在50和90 °C下，NP-PL产生的RS几乎比三个果皮中未经处理的果胶酸裂解酶 (PL) 产生的RS大两倍。在NP-PL处理下，香蕉和柑橘皮的最佳生产是在孵育24和6小时后，马铃薯皮分别在50和90 °C的温度下分别为24和4小时。NP-PL可以脱胶，脱皮的苎麻纤维，并增强纤维的韧性和细度。在加工24和48小时后，纤维的重量损失24% 和31% 更好 (与PL处理相比)。这些发现对生物乙醇，生物燃料和纺织行业具有潜在的影响。