BACKGROUND & AIMS: :So far, the development of a unique strategy for specific biomolecules activity monitoring and precise drugs release in cancerous cells is still challenging. Here, we designed a conformation-switchable smart nanoprobe to monitor telomerase activity and to enable activity-triggered drug release in cancerous cells. The straightforward nanoprobe contained a gold nanoparticle (AuNP) core and a dense layer of 5-carboxyfluorescein (FAM)-labeled hairpin DNA shell. The 3' region of hairpin DNA sequence could function as the telomerase primer to be elongated in the presence of telomerase, resulting in the conformational switch of hairpin DNA. As a result, the FAM fluorescence was activated and the anticancer drug doxorubicin (Dox) molecules which intercalated into the stem region of the hairpin DNA sequence were released into cancerous cells simultaneously. The smart method could specifically distinguish cancerous cells from normal cells based on telomerase activity. It also showed a good performance for monitoring telomerase activity in the cytoplasm by molecular imaging and precise release of Dox triggered by telomerase activity in cancerous cells. These advantages may offer a great potential of this method for monitoring telomerase activity in cancer progression and estimating therapeutic effect.

背景与目标： : 到目前为止，开发用于特定生物分子活性监测和癌细胞中精确药物释放的独特策略仍然具有挑战性。在这里，我们设计了一种构象可切换的智能纳米探针，以监测端粒酶活性并使活性触发的药物在癌细胞中释放。简单的纳米探针包含金纳米颗粒 (AuNP) 核心和5-羧基荧光素 (FAM) 标记的发夹DNA壳的致密层。发夹DNA序列的3' 区域可以用作端粒酶引物，在端粒酶存在下被拉长，从而导致发夹DNA的构象转换。结果，FAM荧光被激活，插入发夹DNA序列茎区的抗癌药物阿霉素 (Dox) 分子同时释放到癌细胞中。smart方法可以根据端粒酶活性特异性区分癌细胞和正常细胞。它还显示出通过分子成像监测细胞质中端粒酶活性以及癌细胞中端粒酶活性触发的Dox精确释放的良好性能。这些优点可能为该方法在癌症进展中监测端粒酶活性和评估治疗效果提供了巨大的潜力。

BACKGROUND & AIMS: :Development of rapid antiviral assays can expedite the process of screening potential agents against viral pathogens. In the present study, fluorescent quantum dots (QDs) incorporated with infectious pancreatic necrosis virus (IPNV) were used as imaging nanoprobes to detect the threshold amount of poly I:C (an interferon inducer) required to induce zebrafish cells into an antiviral state against IPNV. QD-IPNV hybrids were formed by colloidal clustering of negatively charged QDs and IPNV, using the cationic polymer polybrene (50 μg/mL). To test the screening potential of the QD-IPNV hybrids for anti-IPNV drug candidates, zebrafish ZF4 cells primed with the immunostimulant poly I:C at concentrations of 1, 5, and 10 μg/mL for 6h were used as a model system. After poly I:C treatment, cells were exposed to the QD-IPNV hybrids for 6h at a multiplicity of infection (MOI) of 5. The anti-IPNV effectiveness of poly I:C was assessed via fluorescence intensity of the QDs. Our results showed that ZF4 cells primed with poly I:C at 10 μg/mL were highly protected from IPNV challenge (i.e., no detection of QD fluorescence). In summary, a rapid and efficient cell-based imaging platform has been developed for assessing the anti-IPNV activity of poly I:C on ZF4 cells using QD-IPNV hybrids. This approach may be applied to a wider range of fish species and fish pathogenic viruses.

背景与目标： : 快速抗病毒检测的发展可以加快筛选针对病毒病原体的潜在药物的过程。在本研究中，结合了传染性胰腺坏死病毒 (IPNV) 的荧光量子点 (qd) 用作成像纳米探针，以检测将斑马鱼细胞诱导为抗IPNV的抗病毒状态所需的poly I:C (干扰素诱导剂) 的阈值量。使用阳离子聚合物聚乙烯 (50 μ g/mL)，通过带负电荷的量子点和IPNV的胶体聚集形成qd-ipnv杂种。为了测试QD-IPNV杂种对抗IPNV候选药物的筛选潜力，将用免疫刺激剂poly I:C以1、5和10 μ g/mL的浓度引发6小时的斑马鱼ZF4细胞用作模型系统。poly I:C处理后，将细胞以5的多重感染 (MOI) 暴露于QD-IPNV杂种6小时。通过量子点的荧光强度评估poly I:C的抗IPNV有效性。我们的结果表明，以10 μ g/mL的poly I:C引发的ZF4细胞受到IPNV攻击的高度保护 (即，未检测到QD荧光)。总之，已经开发了一种快速有效的基于细胞的成像平台，用于使用qd-ipnv杂种评估poly I:C对ZF4细胞的抗IPNV活性。这种方法可以应用于更广泛的鱼类物种和鱼类致病病毒。

BACKGROUND & AIMS: :The application of intensity-based H2O2-responsive fluorescence nanoprobe for circulating tumor cell detection was limited by the complex background and the nanoprobe uptake in each CTC. In this context, we developed a ratiometric fluorescence nanoprobe, on which a H2O2-responsive subunit and a stable subunit grafted working as a H2O2 detector and a reference, respectively. When responding to intracellular H2O2, the reference fluorescence (580 nm) maintained as a correction background while the detector fluorescence (450 nm) was turned on to conduct CTC enumeration and intracellular H2O2 evaluation. Two normal cells and three colon cancer cells were examined to evaluate their endogenous H2O2 with the ratiometric nanoprobe by flow cytometry and confocal laser scanning microscopy. CTC sample from colorectal cancer patients was used to validate the performance of the nanoprobe for CTC enumeration and H2O2 evaluation. The results indicated that not only CTC could be effectively identified based on the "turn on" fluorescence, but also the viability of the identified CTCs could be assessed with the intensity of the reference fluorescence to avoid the false-positive number. Moreover, the clinical results demonstrated that the viability CTC count combined with intracellular H2O2 content (described as I450/580)were related to the tumor TNM stage, which might provide significant guidance for clinical treatments.

背景与目标： : 基于强度的H2O2-responsive荧光纳米探针在循环肿瘤细胞检测中的应用受到复杂背景和每个CTC中纳米探针摄取的限制。在这种情况下，我们开发了比率荧光纳米探针，在该探针上分别接枝了H2O2-responsive亚基和稳定亚基作为H2O2检测器和参考。当响应细胞内H2O2时，参考荧光 (580纳米) 保持为校正背景，同时开启检测器荧光 (450纳米) 以进行CTC计数和细胞内H2O2评估。通过流式细胞术和共聚焦激光扫描显微镜检查了两个正常细胞和三个结肠癌细胞，以使用比率纳米探针评估其内源性H2O2。使用来自结直肠癌患者的CTC样品来验证纳米探针用于CTC计数和H2O2评估的性能。结果表明，不仅可以根据 “开启” 荧光有效地鉴定CTC，而且可以根据参考荧光的强度评估鉴定的CTC的生存能力，以避免假阳性。此外，临床结果表明，活力CTC计数与细胞内H2O2含量 (描述为I450/580) 与肿瘤TNM分期有关，可为临床治疗提供重要指导。

BACKGROUND & AIMS: :Fabrication and synthesis of plasmonic structures is rapidly moving towards sub-nanometer accuracy in control over shape and inter-particle distance. This holds the promise for developing device components based on novel, non-classical electro-optical effects. Monochromated electron energy-loss spectroscopy (EELS) has in recent years demonstrated its value as a qualitative experimental technique in nano-optics and plasmonic due to its unprecedented spatial resolution. Here, we demonstrate that EELS can also be used quantitatively, to probe surface plasmon kinetics and damping in single nanostructures. Using this approach, we present from a large (>50) series of individual gold nanoparticles the plasmon Quality factors and the plasmon Dephasing times, as a function of energy/frequency. It is shown that the measured general trend applies to regular particle shapes (rods, spheres) as well as irregular shapes (dendritic, branched morphologies). The combination of direct sub-nanometer imaging with EELS-based plasmon damping analysis launches quantitative nanoplasmonics research into the sub-nanometer realm.

背景与目标： : 等离子体结构的制造和合成在控制形状和粒子间距离方面正迅速朝着亚纳米精度发展。这为基于新颖的非经典电光效应开发设备组件提供了希望。近年来，单色电子能量损失谱 (EELS) 由于其前所未有的空间分辨率，已证明其作为纳米光学和等离子体的定性实验技术的价值。在这里，我们证明了EELS也可以定量地用于探测单个纳米结构中的表面等离子体动力学和阻尼。使用这种方法，我们从大量 (>50) 的单个金纳米粒子系列中提出了等离子体激元质量因子和等离子体激元移相时间，作为能量/频率的函数。表明，测得的总体趋势适用于规则的颗粒形状 (杆，球) 以及不规则的形状 (树枝状，分支形态)。直接亚纳米成像与基于EELS的等离激元阻尼分析相结合，将定量纳米等离子体研究引入亚纳米领域。

BACKGROUND & AIMS: :In this study we describe a new methodology to physically probe individual complexes formed between proteins and DNA. By combining nanoscale, high speed physical force measurement with sensitive fluorescence imaging we investigate the complex formed between the prokaryotic DNA repair protein UvrA2 and DNA. This approach uses a triangular, optically-trapped "nanoprobe" with a nanometer scale tip protruding from one vertex. By scanning this tip along a single DNA strand suspended between surface-bound micron-scale beads, quantum-dot tagged UvrA2 molecules bound to these '"DNA tightropes" can be mechanically interrogated. Encounters with UvrA2 led to deflections of the whole nanoprobe structure, which were converted to resistive force. A force histogram from all 144 detected interactions generated a bimodal distribution centered on 2.6 and 8.1 pN, possibly reflecting the asymmetry of UvrA2's binding to DNA. These observations successfully demonstrate the use of a highly controllable purpose-designed and built synthetic nanoprobe combined with fluorescence imaging to study protein-DNA interactions at the single molecule level.

背景与目标： : 在这项研究中，我们描述了一种物理探测蛋白质和DNA之间形成的单个复合物的新方法。通过将纳米级，高速物理力测量与灵敏的荧光成像相结合，我们研究了原核DNA修复蛋白UvrA2与DNA之间形成的复合物。这种方法使用三角形的，光学捕获的 “纳米探针”，其纳米级尖端从一个顶点伸出。通过沿着悬浮在表面结合的微米级珠子之间的单个DNA链扫描该尖端，可以机械地询问与这些 “DNA牵索” 结合的量子点标记的UvrA2分子。与UvrA2的相遇导致整个纳米探针结构的偏转，并将其转换为阻力。来自所有144检测到的相互作用的力直方图产生了以2.6和8.1 pN为中心的双峰分布，这可能反映了UvrA2与DNA结合的不对称性。这些观察结果成功地证明了使用高度可控的目的设计和构建的合成纳米探针结合荧光成像技术在单分子水平上研究蛋白质-DNA相互作用。

BACKGROUND & AIMS: PURPOSE:A complete surgical excision with negative tumor margins is the single most important factor in the prediction of long-term survival for most cancer patients with solid tumors. We hypothesized that image-guided surgery using nanoparticle-enhanced photoacoustic and fluorescence imaging could significantly reduce the rate of local recurrence. METHODS:A murine model of invasive mammary carcinoma was utilized. Three experimental groups were included: (1) control; (2) tumor-bearing mice injected with non-targeted nanoprobe; and (3) tumor-bearing mice injected with targeted nanoprobe. The surgeon removed the primary tumor following the guidance of photoacoustic imaging (PAI), then inspected the surgical wound and removed the suspicious tissue using intraoperative near-infrared (NIR) fluorescence imaging. The mice were followed with bioluminescence imaging weekly to quantify local recurrence. RESULTS:Nanoprobe-enhanced photoacoustic contrast enabled PAI to map the volumetric tumor margins up to a depth of 31 mm. The targeted nanoparticles provided significantly greater enhancement than non-targeted nanoparticles. Seven mice in the group injected with the targeted nanoprobes underwent additional resections based upon NIR fluorescence imaging. Pathological analysis confirmed residual cancer cells in the re-resected specimens in 5/7 mice. Image-guided resection resulted in a significant reduction in local recurrence; 8.7 and 33.3 % of the mice in the targeted and control groups suffered recurrence, respectively. CONCLUSIONS:These results suggest that photoacoustic and NIR intraoperative imaging can effectively assist a surgeon to locate primary tumors and to identify residual disease in real-time. This technology has promise to overcome current clinical challenges that result in the need for second surgical procedures.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. PROCEDURES:The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd(3+) was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. RESULTS:According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T 1 compared to the unlabeled cells. CONCLUSIONS:The results showed that the novel contrast agent could become a useful tool in early detection of cancer.

背景与目标：

BACKGROUND & AIMS: :Abnormal H2O2 levels are closely related to many diseases, including inflammation and cancers. Herein, we simultaneously load HRP and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), into liposomal nanoparticles, obtaining a Lipo@HRP&ABTS optical nanoprobe for in vivo H2O2-responsive chromogenic assay with great specificity and sensitivity. In the presence of H2O2, colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of H2O2 down to submicromolar concentrations. Using Lipo@HRP&ABTS as an H2O2-responsive nanoprobe, we could accurately detect the inflammation processes induced by LPS or bacterial infection in which H2O2 is generated. Meanwhile, upon systemic administration of this nanoprobe we realize in vivo photoacoustic imaging of small s.c. tumors (∼2 mm in size) as well as orthotopic brain gliomas, by detecting H2O2 produced by tumor cells. Interestingly, local injection of Lipo@HRP&ABTS further enables differentiation of metastatic lymph nodes from those nonmetastatic ones, based on their difference in H2O2 contents. Moreover, using the H2O2-dependent strong NIR absorbance of Lipo@HRP&ABTS, tumor-specific photothermal therapy is also achieved. This work thus develops a sensitive H2O2-responsive optical nanoprobe useful not only for in vivo detection of inflammation but also for tumor-specific theranostic applications.

背景与目标： : H2O2水平异常与许多疾病密切相关，包括炎症和癌症。在本文中，我们同时将HRP及其底物2,2 '-叠氮基-双 (3-乙基苯并噻唑啉-6-磺酸) (ABTS) 加载到脂质体纳米颗粒中，获得Lipo @ HRP & ABTS光学纳米探针，用于具有高度特异性和灵敏度的体内H2O2-responsive显色测定。在存在H2O2的情况下，HRP会将无色ABTS转化为具有强近红外 (NIR) 吸光度的氧化形式，从而能够将H2O2的光声检测降至亚微摩尔浓度。使用Lipo @ HRP & ABTS作为H2O2-responsive纳米探针，我们可以准确地检测由LPS或细菌感染引起的H2O2引起的炎症过程。同时，在系统施用该纳米探针后，我们实现了小s.C.的体内光声成像。通过检测肿瘤细胞产生的H2O2，肿瘤 (约2毫米大小) 以及原位脑胶质瘤。有趣的是，根据H2O2含量的差异，局部注射Lipo @ HRP和ABTS进一步使转移淋巴结与非转移淋巴结区分。此外，使用Lipo @ HRP & ABTS H2O2-dependent强的NIR吸光度，还可以实现肿瘤特异性光热治疗。因此，这项工作开发了一种灵敏的H2O2-responsive光学纳米探针，不仅可用于体内检测炎症，而且可用于肿瘤特异性治疗应用。

BACKGROUND & AIMS: PURPOSE:The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. METHODS:A home-made ανβ3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. RESULTS:The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of β3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging. CONCLUSIONS:The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.

背景与目标：

BACKGROUND & AIMS: :Circulating tumor cells (CTCs) represent the most common way of tumor metastasis and has been considered as a significant index for tumor diagnosis, staging and prognosis. However, CTC detection and analysis are always limited by the scarcity of CTC in the peripheral blood and the interference of blood cells. Therefore, here we presented with a hydrogen peroxide (H2O2)-response nanoprobes with CD44-targeted ability to reduce the interference of blood cells and improve the detection efficiency and accuracy and the pancreatic cancer cell was used to evaluate the feasibility of our probe. Shortly, hydrophobic H2O2-response naphthalimide-borate fluorophore was introduced onto the hydrophilic hyaluronic acid to form an amphiphilic complex, which could self-assemble into fluorescent nanoprobes in water. Our studies demonstrated that the nanoprobes were not only able to specifically recognize the pancreatic cancer cells with overexpressed CD44 proteins and reduce the influence of white blood cells in the peripheral blood, but also capable of semi-quantifying H2O2 content in CTCs, Which could be further used as a significant index for tumor clinical evaluation and therapy.

背景与目标： 循环肿瘤细胞 (ctc) 是最常见的肿瘤转移方式，被认为是肿瘤诊断、分期和预后的重要指标。但是，CTC的检测和分析总是受到外周血中CTC的稀缺和血细胞干扰的限制。因此，我们在这里提出了一种过氧化氢 (H2O2) 响应的纳米探针，该探针具有CD44-targeted的能力，可以减少血细胞的干扰并提高检测效率和准确性，并且使用胰腺癌细胞来评估我们的探针的可行性。不久，将疏水H2O2-response萘二酰亚胺-硼酸盐荧光团引入亲水透明质酸上，形成两亲性复合物，该复合物可在水中自组装成荧光纳米探针。我们的研究表明，纳米探针不仅能够特异性识别具有过表达CD44蛋白的胰腺癌细胞并减少外周血中白细胞的影响，而且能够半定量CTCs中的H2O2含量，可进一步作为肿瘤临床评估和治疗的重要指标。

BACKGROUND & AIMS: :Technologies to assess the molecular targets of biomolecules in living cells are lacking. We have developed a technology called magnetism-based interaction capture (MAGIC) that identifies molecular targets on the basis of induced movement of superparamagnetic nanoparticles inside living cells. Efficient intracellular uptake of superparamagnetic nanoparticles (coated with a small molecule of interest) was mediated by a transducible fusogenic peptide. These nanoprobes captured the small molecule's labeled target protein and were translocated in a direction specified by the magnetic field. Use of MAGIC in genome-wide expression screening identified multiple protein targets of a drug. MAGIC was also used to monitor signal-dependent modification and multiple interactions of proteins.

背景与目标： : 缺乏评估活细胞中生物分子分子靶标的技术。我们开发了一种称为基于磁性的相互作用捕获 (MAGIC) 的技术，该技术可根据活细胞内超顺磁性纳米颗粒的诱导运动来识别分子靶标。超顺磁性纳米颗粒 (涂有目标小分子) 的有效细胞内摄取是由可传递的融合肽介导的。这些纳米探针捕获了小分子标记的靶蛋白，并在磁场指定的方向上易位。在全基因组表达筛选中使用MAGIC确定了药物的多个蛋白质靶标。MAGIC还用于监测信号依赖性修饰和蛋白质的多种相互作用。

BACKGROUND & AIMS: :Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intracellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intracellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (mPEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe ("OFF" state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence ("ON" state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors.

背景与目标： 多功能纳米粒子与成像方式 (如磁共振和光学) 和治疗药物集成在一起，是未来癌症诊断和治疗的有希望的候选者。尽管肿瘤细胞的靶向药物递送和成像一直是工程纳米颗粒探针的主要重点，但尚未为开发可以确认和监测细胞内药物释放事件的传感探针做出广泛的努力。在这里，我们介绍了基于量子点 (Qdot)-氧化铁 (IO) 的多峰/多功能纳米复合探针，该探针可光学和磁性成像，可靶向并能够报告细胞内药物释放事件。具体来说，该探针由装饰有卫星CdS的超顺磁性氧化铁纳米颗粒核 (IONP) 组成: Mn/ZnS Qdots，其中Qdots本身被STAT3抑制剂 (一种抗癌剂)，维生素叶酸 (作为靶向基序) 和m-聚乙二醇 (mPEG，一种亲水性分散剂)。由于涉及IONP，叶酸和STAT3试剂的结合的电子/能量转移介导的猝灭过程，Qdot发光在该纳米复合探针中被猝灭 (“关闭” 状态)。细胞内摄取后，探针暴露于含有胞质谷胱甘肽 (GSH) 的环境中，从而恢复了Qdot发光 (“ON” 状态)，从而报告了摄取和药物释放。使用荧光和MR测量以及使用过表达叶酸受体的癌细胞的体外研究验证了探针的功能。

BACKGROUND & AIMS: :In breast cancer, a proper biomarker for the assessment of metastasis and poor prognosis is the RNA of activated leukocyte cell adhesion molecule (ALCAM) gene, which is expressed at high levels in breast tumor. We applied DNA-functionalized gold nanoparticles as the target-specific probes, for detecting specific sequences of DNA or RNA. At high MgCL2 concentrations, nanoprobes aggregate in the absence of the complementary DNA sequence and alteration in the solution color is detectable by evaluating the localized surface plasmon resonance (LSPR). But in the presence of complementary DNA, nanoprobes hybridize to the complementary sequence; therefore, no aggregation takes place, and no color change is observed. We designed a gold nanoprobe-based method that promptly detects the ALCAM gene expression in a low reaction volume with high sensitivity and specificity. This method is simple, fast, selective, and quantitative and can be done with small concentrations of the target (fmol/μL). Limit of detection of the method corresponded to 300 fmol/μL of synthetic ALCAM target.

背景与目标： : 在乳腺癌中，用于评估转移和不良预后的适当生物标志物是活化的白细胞细胞粘附分子 (ALCAM) 基因的RNA，该RNA在乳腺肿瘤中高水平表达。我们使用DNA功能化的金纳米颗粒作为靶标特异性探针，用于检测DNA或RNA的特定序列。在高MgCL2浓度下，纳米探针在没有互补DNA序列的情况下聚集，并且通过评估局部表面等离子体共振 (LSPR) 可以检测到溶液颜色的改变。但是在存在互补DNA的情况下，纳米探针与互补序列杂交; 因此，没有发生聚集，也没有观察到颜色变化。我们设计了一种基于金纳米探针的方法，该方法可在低反应体积下以高灵敏度和特异性快速检测ALCAM基因表达。该方法简单，快速，选择性和定量，可以用小浓度的靶标 (fmol/μ l) 完成。该方法的检测限相当于合成ALCAM靶的300  fmol/μ l。

BACKGROUND & AIMS: :A novel electrochemical immunosensor for tumor biomarker detection based on three-dimensional, magnetic and electroactive nanoprobes was developed in this study. To fabricate the nanoprobes, negatively charged Fe(3)O(4) nanoparticles (Fe(3)O(4) NPs) and gold nanoparticles (Au NPs) were first loaded on the surface of multiple wall carbon nanotubes (MCNTs) which were functioned with redox-active hemin and cationic polyelectrolyte poly(dimethyldiallylammonium chloride) (PDDA). Using alpha fetoprotein (AFP) as a model analyte, AFP antibody (anti-AFP) was absorbed on the surface of Au NPs, bovine serum albumin (BSA) was then used to block sites against non-specific binding, and finally formed anti-AFP/Au NPs/Fe(3)O(4)/hemin/MCNTs named anti-AFP nanoprobes. When the target antigen AFP was present, it interacted with anti-AFP and formed an antigen-antibody complex on the nanoprobe interface. This resulted in a decreased electrochemical signal of hemin for quantitative determination of AFP when immobilized onto the screen-printed working electrode (SPCE). The results showed that the nanoprobe-based electrochemical immunosensor was sensitive to AFP detection at a concentration of 0.1 to 200 ng·mL(-1) with a detection limit of 0.04 ng·mL(-1), it also demonstrated good selectivity against other interferential substances. The electroactive nanoprobes can be massively prepared, easily immobilized on the SPCE for target detection and rapidly renewed with a magnet. The proposed immunosensor is fast, simple, sensitive, stable, magnet-controlled, nontoxic, label-free and reproducible.

背景与目标： : 本研究开发了一种基于三维，磁性和电活性纳米探针的用于肿瘤生物标志物检测的新型电化学免疫传感器。为了制造纳米探针，首先将带负电的Fe(3)O(4) 纳米颗粒 (Fe(3)O(4) NPs) 和金纳米颗粒 (Au NPs) 负载在具有氧化还原活性的血红素和阳离子聚电解质聚 (二甲基二烯丙基氯化铵) (PDDA)。以甲胎蛋白 (AFP) 为模型分析物，AFP抗体 (anti-AFP) 被吸收在Au NPs表面，牛血清白蛋白 (BSA) 被用于阻断位点对抗非特异性结合，最后形成了名为抗AFP/Au NPs/Fe(3)O(4)/hemin/MCNTs的抗AFP纳米探针。当目标抗原AFP存在时，它与抗AFP相互作用，并在纳米探针界面上形成抗原-抗体复合物。当固定在丝网印刷的工作电极 (SPCE) 上时，这导致用于定量测定AFP的血红素的电化学信号降低。结果表明，基于纳米探针的电化学免疫传感器在0.1 ~ 200 ng·mL(-1) 浓度下对AFP检测敏感，检出限为0.04 ng·mL(-1)，对其他干扰物质具有良好的选择性。电活性纳米探针可以大量制备，易于固定在SPCE上进行目标检测，并用磁铁快速更新。所提出的免疫传感器具有快速，简单，灵敏，稳定，磁体控制，无毒，无标记和可重现性。

BACKGROUND & AIMS: :The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic-photothermal, therapeutic, and radiotherapeutic potential of 177Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu-DenAuNP-folate-bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP-folate-bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP-folate-bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the 177Lu-DenAuNP-folate-bombesin plasmonic properties. After treatment with 177Lu-DenAuNP-folate-bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The 177Lu-DenAuNP-folate-bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic-photothermal therapy, and targeted radiotherapy.

背景与目标： : 将荧光和等离子体性质整合到一个分子中对于开发多功能成像和治疗纳米探针至关重要。这项研究的目的是评估177Lu-dendrimer在树突状腔 (177Lu-DenAuNP-folate-bombesin) 中与叶酸和金纳米颗粒缀合的177Lu-dendrimer的荧光特性以及等离子体光热，治疗和放射治疗潜力。它在T47D乳腺癌细胞中内化。从细胞内的缀合物在825 nm处发射的强烈近红外 (NIR) 荧光证实了DenAuNP-叶酸-蛙皮素在光学成像中的有用性。激光照射后，细胞中纳米系统的存在导致培养基温度显着升高 (46.8 °C，与没有DenAuNP-叶酸-蛙皮素的39.1 °C相比，P <0.05)，由于177Lu-DenAuNP-folate-bombesin的等离子体特性，导致细胞活力显着降低 (降至16.51% ± 1.52%)。用177Lu-DenAuNP-folate-bombesin处理后，由于在细胞内传递的辐射吸收剂量 (63.16 ± 4.20 Gy)，T47D细胞活力90% 降低。在癌细胞中内化的177Lu-DenAuNP-folate-bombesin纳米探针表现出适用于光学成像，等离子体-光热疗法和靶向放射治疗的特性。