量子点技术在神经退行性疾病诊断中的应用

近年来,随着我国逐步进入老龄化社会,神经退行性疾病发病率逐年升高,其具有诊治难、预后差等特点,因此早期快速诊断能提高治疗效果,大大降低医疗负担。神经退行性疾病的传统诊断方法需依赖大型仪器,漏诊率较高,且相关生物标志物检测耗时较长。量子点作为一种具有独特性质的新型荧光标记材料在神经退行性疾病血清学诊断方面具有极大应用潜力,其适于多标志物联合检测的特点可提高诊断灵敏度和特异性,且量子点与微流控技术相结合进一步拓展了其在神经退行性疾病诊断中的应用。该文梳理了量子点技术的特点及其近年来在神经系统疾病诊断中的应用,并对其未来发展趋势进行了展望。     

石墨烯量子点的生物学应用

石墨烯量子点是石墨烯家族的衍生物,石墨烯量子点除了具有石墨烯的优良性能,还具有量子限制效应和边界效应所产生的一系列新的特性,因此吸引了各领域科学家的广泛关注。石墨烯量子点这类新颖材料的研究在这两三年内,无论是实验还是理论方面均取得了极大进展。石墨烯量子点生物相容性好,能够光致发光,具有光电特性,可用于生物成像和生物传感器。作者着重探索石墨烯多样的生物学应用,并从石墨烯量子点的发展、特性、制备方法、修饰、生物学应用、生物安全性等方面进行综述。     

量子点的表面修饰、表征及其活细胞成像研究

目的 通过对疏水性量子点表面进行亲水性改造并偶联单克隆抗体,制备免疫荧光探针用于细胞荧光标记示踪.方法 将牛血清白蛋白(BSA)作为乳化剂分子对疏水性量子点进行表面亲水性改造,检测亲水性改造后的量子点物理特性,采用MTT法测定其对细胞活力的影响.将亲水性改造后的量子点与trastuzumab偶联,对HER-2阳性乳腺癌细胞进行实时荧光成像检测.结果 经亲水性改造后的量子点粒径约70nm,分布较均一;在不同离子强度和pH环境中,仍保持良好的发光性能和胶体稳定性;生物相容性佳,未检测到明显细胞毒作用;经表面偶联肿瘤特异性单克隆抗体后,成功地对HER-2阳性乳腺癌细胞进行了长时间的活细胞跟踪成像研究.结论 亲水性量子点可通过选择性偶联抗体获得免疫量子点荧光探针,从而对细胞、组织等进行特异性荧光成像和检测.     

原发性气管肿瘤并皮下气肿的影像评价

目的 :探讨计算机X线摄影 (CR)对原发性气管肿瘤 (PTT)并皮下气肿的诊断价值 ;同时讨论了良、恶性肿瘤的表现 ,普通CR体层、CT和MRI在诊断PTT中的优、缺点和选择。方法 :6例病人均行高千伏胸部摄影及纤支镜检查 ,5例病人行坐位气管体层 ;因病人不能平卧均未做CT检查。结果 :CR体层摄影可清楚显示肿瘤的部位、大小及与管壁的关系 ,其中腺瘤 3例 ,鳞癌、腺癌和纤维瘤各 1例。结论 :普通CR体层摄影是气管肿瘤首选检查方法 ,有很高的诊断价值 ;病情允许仍应选择CT检查。     

CD147分子及其与肿瘤关系的研究进展

肿瘤的浸润、转移是一个多因素参与、多步骤的复杂过程,其中包括基底膜降解、基质渗透以及肿瘤细胞进出血管和对靶组织的侵袭。已证实CD147分子能刺激肿瘤细胞周围的成纤维细胞产生基质金属蛋白酶,促进肿瘤的浸润和转移,并在肿瘤的早期诊断、治疗及预后等方面具有重要的临床意义,其与肿瘤的关系是目前研究的热点。本文综述了CD147分子及其与肿瘤关系的研究进展。     

磁性纳米氧化铁粒子在肿瘤影像及治疗中的应用及进展

磁性纳米氧化铁粒子是指直径在纳米范围的氧化铁粒子,具有化学性质稳定、血液滞留时间长、低毒性、顺磁性、生物可降解性等特点,可通过静电作用或化学作用耦联多肽、单克隆抗体、化疗药物、基因片段等靶肿瘤功能分子,因而在肿瘤影像、治疗、研究中有着广泛的应用.该文对近年来磁性纳米氧化铁粒子在肿瘤影像及治疗中的应用及进展进行了评述.     

门静脉栓塞的MSCT诊断价值

目的:探讨门静脉栓塞的MSCT诊断价值。方法:回顾性分析29例经临床/手术病理证实的门静脉栓塞患者的MSCT表现和临床资料,29例中门静脉血栓(PVT)13例(PVT组),门静脉瘤栓(PTT)16例(PTT组)。结果:29例栓子的部位、范围均清晰显示;13例PVT中9例继发于肝硬化门静脉高压;CT平扫呈等或稍高密度,动态增强呈不同形态、无强化的低密度充盈缺损;7例呈典型的"靶征",5例呈"线样征"。16例PTT均继发于肝癌;CT平扫表现为等或稍低密度,动态增强呈形态各异、不均匀强化的充盈缺损;PVT组与PTT组间CT强化差异具有统计学意义(P=0.000);PVT组完全阻塞3例(3/13),PTT组12例(12/16),PTT组完全阻塞率高于PVT组(P=0.040);PVT组管腔局部扩张2例(2/13),PTT组12例(12/16),PTT组管腔局部扩张高于PVT组(P=0.030);PVT组管壁局部不光整1例(1/13),PTT组14例(14/16),PTT组管壁局部不光整率高于PVT组(P=0.000)。结论:MSCT能显示门静脉栓塞的影像特征,准确判断栓子的部位、范围及性质,对该病的诊断具有重要价值。     

丹红注射液治疗脑梗死多靶点药物机理研究

目的探讨脑梗死患者经丹红注射液治疗前后血清氧化低密度脂蛋白（Ox-LDL）、基质金属蛋白酶2（MMP-2）、肿瘤坏死因子（TNF-α）的测定,观察丹红注射液对急性脑梗死治疗的多靶点药物机理。方法选择在我院住院治疗的急性脑梗死患者15例,给予0.9%生理盐水250ml加丹红注射液40ml每日1次静点,且在入院时及药物治疗后2周分别检测血清氧化低密度脂蛋白、基质金属蛋白酶及肿瘤坏死因子的抗体水平。结果丹红注射液治疗前检测Ox-LDL（43.94±25.20）μg/dl、MMP-2（25.84±14.10）μg/dl、TNF-α（56.41±31.86）μg/dl及治疗后检测Ox-LDL（31.25±24.45）μg/dl、MMP-2（21.12±7.82）μg/dl、TNF-α（42.90±12.04）μg/dl,治疗前后血清含量有显著变化（P〈0.05）。结论丹红注射液从抗氧化、抗炎症反应的角度,对急性脑梗死的多靶点治疗起重要作用。     

肾透明细胞癌CT灌注成像特点的研究

目的:探讨肾透明细胞癌灌注成像的特点及临床应用价值。方法:37例经过手术病理证实的肾透明细胞癌患者(肿瘤生长部位均靠近肾门附近),术前均选择近肾门层面进行动态增强扫描,经过灌注软件处理分析分别获得肾癌组织及双侧肾皮质的血流量(BF)、血容量(BV)、平均通过时间(MTT)、组织通透性(PS)及时间密度曲线(TDC图)。结果:肾透明细胞癌肿瘤最高密度点血供丰富,但血流量较对侧正常皮质仍较低;肿瘤平均灌注较两侧皮质均低;肿瘤同侧肾脏皮质灌注较对侧低;肿瘤内不同密度点灌注特性不同;不同分级的肿瘤对静脉血流有不同的影响。结论:肾透明细胞癌CT灌注成像具有一定的特点,对其诊断及肾血流的评估具有一定的价值。     

肿瘤血管生成的PET检测

肿瘤血管生成作为肿瘤的主要特征,在肿瘤生长和转移中起着重要作用,为肿瘤治疗提供了新策略.通过标记血管生成相关的受体、多肽、激酶或细胞外基质蛋白,形成高亲和力的分子探针,与肿瘤血管生成过程中产生的特异性靶分子结合,从而显示包括整合素、VEGF/VEGFR、基质金属蛋白酶(MMPs)等与血管生成关系密切的特征性血管生成因子,可从分子水平对肿瘤新生血管及血管靶向治疗疗效进行无创性检测.笔者就肿瘤血管生成PET影像学检测研究进展及未来发展作一综述.     

Gold nanoparticles-based photothermal therapy for breast cancer

AuNPs-mediated photothermal therapy (PTT) is gaining popularity in both laboratory research and medical applications. It has proven clear advantages in breast cancer therapy over conventional thermal ablation because of its easily-tuned features of irradiation light with inside hyperthermia ability. Notwithstanding this significant progress, the therapeutic potential of AuNPs-mediated PTT in cancer treatments is still impeded by several challenges, including inherent non-specificity, low photothermal conversion effectiveness, and the limitation of excitation light tissue penetration. Given the rapid progress of AuNPs-mediated PTT, we present a comprehensive overview of significant breakthroughs in the recent advancements of AuNPs for PTT, focusing on breast cancer cells. With the improvement of chemical synthesis technology, AuNPs of various sizes and shapes with desired properties can be synthesized, allowing breast cancer targeting and treatment. In this study, we summarized the different sizes and features of four major types of AuNPs in this review: Au nanospheres, Au nanocages, Au nanoshells, and Au nanorods, and explored their benefits and drawbacks in PTT. We also discussed the diagnostic, bioconjugation, targeting, and cellular uptake of AuNPs, which could improve the performance of AuNP-based PTT. Besides that, potential challenges and future developments of AuNP-mediated PTT for clinical applications are discussed. AuNP-mediated PTT is expected to become a highly promising avenue in cancer treatment in the near future.     

Imaging Guided PTT-PDT Combination Therapy of Prostate Cancer Utilizing Ag2S-Fe3O4 Hybrid Nanoparticles and 5-ALA

Superparamagnetic iron oxide nanoparticles (SPIONs) and luminescent semiconductor quantum dots (QDs) have been at the center of biomedicinal research in the last decades, utilized for imaging, diagnostics, and therapy. SPIONs are known and utilized for magnetic resonance imaging (MRI), magnetic hyperthermia and photothermal therapy (PTT) and drug delivery [1, 2]. QDs, on the other hand, are very well established in the bioimaging and theranostics as an alternative to organic fluorophores due to their unique properties such as narrow emission bands, size-tunable and strong fluorescence and excellent photostability [3, 4]. Light-induced localized therapies, namely photodynamic therapy (PDT) and PTT, emerge as an alternative and/or complementary treatments along with conventional chemotherapy in the field of cancer therapeutics [5, 6]. Hybrid nanoparticles composed of magnetic-luminescent properties are highly appealing as they provide dual-imaging ability and enhanced photothermal properties, along with being excellent drug delivery vehicles [7]. In this study, luminescent-superparamagnetic Ag₂S-Fe₃O₄ (AS-SPION) hybrid nanoparticles were developed via a simple ligand exchange method using 2-mercaptopropionic acid (2-MPA) coated AS QDs replacing lauric acid (LA) coating on SPIONs. Synthesis of both particles and the hybrids were previously reported [8, 9]. Final hybrids were then loaded with 5-aminolevulinic acid (5-ALA), which is an FDA approved natural precursor of PDT agent protoporphyrin IX (PPIX), to achieve imaging guided enhanced PDT-PTT combination therapy on prostate cancer cells. By loading 5-ALA to nanoparticles, its bioavailability and the efficiency of the combination therapy can be increased. The hydrodynamic size of the hybrids were less than 100 nm and they had strong emission in the medical imaging window (850-900 nm). The comparative PTT potential of the QDs vs. hybrids were initially investigated in the solution by irradiating the samples at 640 nm (215 mW) and 808 nm (400 mW) at different Ag concentrations. After determining the optimal PTT conditions in the solution, followed by in-vitro dark cytotoxicity of AS-2MPA QDs, AS-SPION hybrids, free ALA, and AS-SPION-ALA particles for LnCap, PC3 and Du145 cell lines, best treatment parameters were defined. Additionally, L929 cells were used to prove the non-toxic nature of the particles. PDT-PTT combination therapy was applied via co-irradiation of the cells with 640 and 808 nm laser at 300 mW and 700 mW power, respectively, for 5 minutes and cell death was evaluated with standard MTT assay. Additionally, cell death mechanisms were investigated in terms of ROS generation, apoptosis/necrosis and live/dead imaging. This study was focused on the determination of advantages of having hybrid nanoparticles providing dual-modality, enhanced phototherapy effect and the difference generated from combination therapy in comparison to monotherapies in the treatment of prostate cancer.     

Theranostic Silver Chalcogenide Quantum Dots in Phototherapy

Nanoparticles entered the phototherapy arena as photosensitizers and as delivery vehicles of organic photosensitizers. Luminescent Ag-chalcogenide quantum dots trigger PTT at long wavelengths and offer image-guided phototherapy. These nanoparticles also effectively deliver organic photosensitizers such as 5-aminolevulinic acid (ALA) and/or drugs to the target, hence provide PDT/PTT, Chemo/PTT, or even Chemo/PDT/PTT combination for effective killing of tumor cells.Nanoparticles entered the phototherapy arena as photosensitizers and as delivery vehicles of organic photosensitizers. 4-Aminolevulinic acid is now an FDA-approved pro-drug for PDT suffering from low bioavailability. Small theranostic nanoparticles that are already under heavy investigation for drug delivery and tracking offer the opportunity to improve ALA-bioavailability and delivery to targets, such as the tumor mass.Ag₂S quantum dots are luminescent in the NIR and highly biocompatible, hence are excellent for delivering ALA and providing image-guided PDT. We have loaded Ag₂S with ALA and tagged it with Cetuximab for improved and selective PDT of EGFR(+) colorectal cancer cells under 420 nm and 630 nm irradiation [1]. This enabled improved PDT with a significantly low ALA dose: 0.17 mM ALA-1 min – 640 nm irradiation caused more than 80% death in SW480 cell line after a short incubation. Further toxicity was obtained with additional 5FU conjugation to these QDs and almost all cells were killed at and above 0.35 mM ALA/15 μg mL⁻¹ 5FU doses, which is dramatically lower than IC50 of each component. Ag₂S QDs were also discovered as photosensitizers for PTT [3,4] and a combination of image-guided PTT and chemotherapy potential was investigated in cancer cells, using folic acid tagged Ag₂S QDs loaded with methotrexate [2]. This approach provided selective and near complete killing of FR(+) HeLa cells compared to HT29 and A549 cells via necrosis/late apoptosis after 10 min irradiation at 808 nm. IC₅₀ of MTX was reduced from 10 to 0.21 μg/mL.Lastly, in vivo examples of chemo/PTT combinations for the treatment of breast cancer will be shown.     

Multifunctional nanoplatform based on g-C3N4, loaded with MnO2 and CuS nanoparticals for oxygen self-generation photodynamic/photothermal synergistic therapy

Photodynamic therapy (PDT) and photothermal therapy (PTT) are both promising therapeutic approaches for cancer. Unfortunately, the anticancer efficiency of PDT is restricted by the hypoxic tumor microenvironment and the performance of the photosensitizer (PS) while the efficiency of PTT is limited by the penetration depth of NIR light, making it difficult to further improve the efficiency of the treatment. In this paper, we strategically proposed a multifunctional nano-platform based on g-C₃N₄ and loaded with CuS and MnO₂ nanoparticals. Interestingly, the obtained F127@CNs-CuS/MnO₂ nano-platform with high singlet oxygen quantum yield and excellent photothermal performance were used in synergistic PTT and PDT therapy to cope with the limitation of single mode cancer treatment under irradiation and has greatly improved the treatment effect. Additionally, MnO₂ nanoparticles loaded on the CNs surface could not only generate oxygen to ameliorate hypoxia in the tumor environment by reacting with H₂O₂ in tumor cells, but also react with the over-expressed reduced glutathione (GSH) in cancer cells to further improve the synergistic therapeutic effect. In the in vitro hepatocarcinoma cell inactivation experiment, the maximum cell inactivation efficiency of the PDT, PTT and PDT/PTT synergistic treatment group reached at 65% (F127@CNs-MnO₂), 69.2% (CNs-MnO₂) and 88.6% (F127@CNs-MnO₂) respectively, which means that the F127@CNs-CuS/MnO₂-mediated PTT/PDT synergy anticancer treatment was more effective than single mode therapy. In summary, the innovative multifunctional nanoplatform F127@CNs-CuS/MnO₂ used for synergistic PTT and PDT treatment has greatly improved the inactivation efficiency of cancer cells and has provided a new scheme for the treatment of hypoxic tumors.     

Local photothermal/photodynamic synergistic antibacterial therapy based on two-dimensional BP@CQDs triggered by single NIR light source

Pathogenic bacteria-infected wound healing faces challenges even though many advanced antibiotics and antibacterial nanoagents have been developed. Herein, we established a two-dimensional antibacterial nanoplatform with synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antibacterial capabilities mediated by a single 808 nm laser irradiation. The nanoplatform is constructed by combining black phosphorus (BP) obtained by liquid phase exfoliation and hydrothermally prepared tellurium-doped carbon quantum dots (CQDs) prepared by electrostatic interaction. As a result, the photothermal conversion of BP and hydroxyl radical (‧OH) production of CQDs under NIR laser makes the nanoplatform (BP@CQDs) possess an outstanding antibacterial performance against S. aureus and E. coli (as high as 92.7% and 98.4%, respectively), resulting in a faster wound closure ratio than another infected wound. Moreover, in vitro and in vivo researches showed that BP@CQDs have good hemocompatibility, cytocompatibility, and biocompatibility during the therapeutic process. This work demonstrates the broad application prospect of BP nanosheets in infectious microenvironments and develops a potential strategy for S. aureus-infected wound repair.     

Gadolinium‐labeled quantum dots for molecular magnetic resonance imaging: R1 versus R2 mapping

Quantum dots labeled with paramagnetic gadolinium chelates can be applied as contrast agent for preclinical molecular MRI combined with fluorescence microscopy. Besides increasing the longitudinal relaxation rate, gadolinium‐labeled quantum dots may increase the transverse relaxation rate, which might be related to their magnetic properties. Furthermore, molecular MRI experiments are primarily conducted at high magnetic fields, where longitudinal relaxation rate becomes less effective, and the use of transverse relaxation rate as a source of contrast may become attractive. Consequently, the optimal method of contrast enhancement using gadolinium‐labeled quantum dots is a priori unknown. The objective of this study was to compare longitudinal relaxation rate– and transverse relaxation rate–based contrast enhancement, proton visibility, and changes thereof induced by gadolinium‐labeled quantum dots targeted to the angiogenic vasculature of murine tumors, using in vivo longitudinal and transverse relaxation rate mapping. At a field strength of 7 T, longitudinal relaxation rate–based measures were superior to transverse relaxation rate–based measures in detecting both the level and spatial extent of contrast agent–induced relaxation rate changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Fabrication of FA/HA-functionalized carbon dots for human breast cancer cell targeted imaging

Green fluorescent carbon dots (CDs) were prepared by one-step hydrothermal method and then modified into folic acid functionalized carbon dots (FA-CDs) and hyaluronic acid functionalized carbon dots (HA-CDs) with targeted function to study their application in breast cancer cells imaging. The microstructure of the CDs observed through TEM showed the CDs with a scale of 2.69 nm. FT-IR and XPS showed the changes of bonds and functional groups that confirmed the transformation of COOH and NH₂ to amide bonds. FA-CDs and HA-CDs had good water solubility and cytocompatibility, which laid a foundation for their application in human breast cancer cells imaging. At the same time, FA-CDs and HA-CDs had strong fluorescence excitation, and the optimal emission wavelength was about 450 nm. In fluorescence imaging of cells, carbon dots had bright green fluorescence in both breast cancer cells (MCF-7 cells) and normal cells (EC cells). After targeted endocytosis, FA-CDs and HA-CDs could emit bright green fluorescence in cancer cells but could not in normal cells, which proved that the synthesized FA-CDs and HA-CDs had targeting properties. FA-CDs and HA-CDs could be used to accurately identify breast cancer cells and normal cells as cancer diagnosis material, which had the potential application in early cancer diagnosis.     

Carbon nitride nanomaterials with application in photothermal and photodynamic therapies

Phototherapies offer treatment of tumors with high spatial selectivity. Photodynamic therapy (PDT) consists in the administration of a photosensitizer (PS) followed by local photoirradiation with light of specific wavelength. The excited states of the PS interact with biomolecules and molecular oxygen producing reactive oxygen species (ROS), which initiate cell death. Photothermal therapy (PTT) employs photothermal agents to harvest the energy from light and convert it into heat to produce a temperature increase of the surrounding environment leading to cell death.Due to their good biocompatibility and unique photophysical properties, carbon-based materials are suitable for application in PDT and PTT. In particular, graphitic carbon nitride (g-C₃N₄), is a low-cost, non-toxic, and environment-friendly material, which is currently being used in the development of new nanomaterials with application in PDT and PTT.This brief review includes recent advances in the development of g-C₃N₄-based nanomaterials specifically designed for achieving red-shifted band gaps with the aim of generating oxygen molecules via water splitting upon red light or NIR irradiation to tackle the hypoxic condition of the tumor area. Nanomaterials designed for theranostics, combining medical imaging applications with PDT and/or PTT treatments are also included. The recent developments of g-C₃N₄-nanomaterials containing lanthanide-based upconversion nanoparticles are also covered. Finally, g-C₃N₄-based nanomaterials employed in microwave induced photodynamic therapy, sonodynamic therapy, and magnetic hyperthermia are considered.     

CuS nanoagents for photodynamic and photothermal therapies: Phenomena and possible mechanisms

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been emerging as attractive and promising methods for tumor treatment in clinical approaches. CuS nanoparticles are effective and cost-effective agents for PTT. Recently, it was observed that CuS nanoparticles are also excellence candidates for PDT. However, the mechanisms for CuS nanoparticles as PDT agents have never been discussed. The goal here is to explore the killing mechanisms of CuS nanoparticles as PTT and PDT agents. CuS nanoparticles were synthesized by a simple wet chemistry method by coating with amphiphilic polymer and examined for their therapeutic potential on lung adenocarcinoma cell line SPC-A-1 in vitro and in vivo using a murine cancer model. The CuS nanoparticles produce heat as well as reactive oxygen species (ROS) when excited by 808 nm laser and show strong anticancer effects both in vitro and in vivo. The heating effects and release of copper ions from CuS upon heating in the tumor acidic environments are the main mechanisms for the generation of reactive oxygen species which are lethal bullets for cancer destruction. As a dual-function agent for PTT and PDT, CuS nanoparticles are promising phototherapy agents for cancer treatment.     

基于荧光碳点的免疫荧光探针构建及其对大肠杆菌的特异性识别

目的：将碳点（ CDs）应用在免疫荧光探针成为取代传统荧光染料的新型标记物。方法通过微波加热方法制备高强荧光碳点,并通过EDC偶联法与大肠杆菌抗体结合形成复合免疫荧光探针,以大肠杆菌O157∶H7为检测模型进行特异性识别实验。结果碳点成功应用在免疫标记大肠杆菌O157∶H7,并可见多色荧光。结论免疫荧光探针成功地识别大肠杆菌O157∶H7,表明碳点可作为免疫荧光探针的荧光标记物,有望制成具有自主知识产权的新型低毒生物传感器。