Recent progress in the green synthesis of rare-earth doped upconversion nanophosphors for optical bioimaging from cells to animals

Rare-earth doped upconversion nanophosphors (UCNPs), which convert low energy near-infrared (NIR) photons into high energy photons such as ultraviolet, visible light and NIR light, have found various applications in optical bioimaging. In this review article, we summarize recent advances in the synthesis and applications of UCNPs achieved by us and other groups in the past few years. The approaches for the synthesis of UCNPs are presented, with an emphasis on the role of green chemistry in the advancement of this field, followed by a focused overview on their latest applications in optical bioimaging from subcellular structures through cells to living animals. Challenges and opportunities for the use of UCNPs in biomedical diagnosis and therapy are discussed.     

NIR‐responsive nanomaterials and their applications; upconversion nanoparticles and carbon dots: a perspective

Near‐infrared (NIR) light responsive materials have received much attention for diverse applications due to their excellent optical properties. This type of material exhibits upconverted luminescence, a non‐linear optical process in which two or more low energy photons, usually from NIR light irradiation are transformed to high energy photons emission through energy transfer upconversion, excited state absorption, photon avalanche or multiphoton absorption. The NIR range of excitation source is favorable for biological imaging and cancer theranostic applications due to their high penetration depth, low autofluorescence, minimal light scattering, reduced photodamage, and negligible phototoxicity. Having these properties, NIR responsive materials such as upconversion nanoparticles (UCNPs) and carbon dots (CDs) which perform upconversion luminescence are actively exploited in a wide variety of applications such as display and sensory technology. While CDs are well known for their versatility in using different chemicals and green precursors to achieve tunable optical properties, UCNPs also have the advantage that a continuous‐wave NIR laser can be used as the excitation source. This article reviews the properties of these two materials in the aspects of luminescence mechanisms and their recent developments in cancer theranostics, display technology, biosensing and metal ions sensing applications. © 2018 Society of Chemical Industry     

上转换发光材料在不同防伪领域的研究进展Q

稀土上转换纳米粒子（UCNPs）能够吸收低能量的红外光并转换为高能量的紫外或可见光,其具有自体发光背景低、发光颜色可调、荧光寿命长和光稳定性好等优异的光学性能,此外,其还具有可加工性高、表面功能化便捷等特点,因而如今已经成为了荧光防伪技术的研究前沿和研究热点,应用前景十分广泛。本文综述了UCNPs的发光机制和一系列制备方法并分析优缺点,阐述了近年来其在标签、图案、编码等荧光防伪领域应用的相关优秀研究成果。进一步地,还探讨了UCNPs在荧光防伪领域应用上所存在的问题和面临的挑战,提出了未来可能的发展方向。     

上转换发光材料在不同防伪领域的研究进展Q

稀土上转换纳米粒子(UCNPs)能够吸收低能量的近红外光并转换为高能量的紫外或可见光,具有自体发光背景低、发光颜色可调、荧光寿命长和光稳定性好等优异的光学性能,还具有可加工性高、表面功能化便捷等特点,已成为荧光防伪技术的研究前沿和研究热点,应用前景广泛.该文综述了UCNPs的发光机制和制备方法,阐述了近年来其在标签、图案、编码等荧光防伪领域应用的相关研究成果.进一步地探讨了UCNPs在荧光防伪领域应用上所存在的问题和面临的挑战,提出了未来可能的发展方向.     

香豆素类荧光传感器检测金属离子的研究进展

金属离子对自然环境和生物体的生长发育具有重要的影响,因此对环境中及生物体内的金属离子的识别和检测正日益受到人们广泛的关注。在不同的分析方法中,荧光分析法具有灵敏度高、选择性好和实时原位检测等优点,是实现环境中和生物体内金属离子识别和检测的良好工具。本文综述了近5年来香豆素类荧光传感器对一些重金属离子（Hg2+、Pb2+、Cd2+、Ni2+、Ag+）和一些具有重要生物学意义的过渡金属离子（Cu2+、Zn2+、Fe3+）的识别与检测及其应用进展情况,着重介绍了传感器分子的设计合成、识别机理、传感特性及其在环境分析和生物检测中的应用。随着金属离子检测要求的提高,未来香豆素类荧光传感器的设计将向着灵敏度更高、选择性更好、抗干扰性能更强的方向发展。此外,香豆素类传感器在生物检测中的应用研究有望得到进一步发展。     

Water-soluble NaYF4:Yb/Er upconversion nanophosphors: Synthesis,characteristics and application in bioimaging

Water-soluble and citrate (cit) coated rare-earth upconversion nanophosphors (UCNPs) were prepared by an efficient surface ligand exchange of the oleic acid capped hydrophobic UCNPs in diethylene glycol (DEG) at high temperature. The successful surface ligand exchange of the UCNPs with citrate was confirmed by Fourier-transform infrared (FTIR) spectroscopy. Further characterizations such as TEM and XRD showed that the ligand exchange reaction had no obvious influence on chemical properties of UCNPs, such as morphology and crystallization. Furthermore, bright UC luminescence was observed when UCNPs-labeled cells were excited with 980nm near-infrared (NIR) light proving that Cit-UCNPs can be used as non-specific labels for imaging HeLa cells. These results indicate that the Cit-UCNPs are a promising candidate for use as bioimaging probes.     

Bioluminescence Resonance Energy Transfer (BRET)-coupled Annexin V-functionalized Quantum Dots for Near-Infrared Optical Detection of Apoptotic Cells

Deregulation in apoptosis induces numerous diseases such as cancer, cardiovascular, and neurodegenerative diseases. Detection of apoptotic cells is crucial for understanding the mechanism of these diseases and for therapy development. Although optical imaging using visible-emitting fluorescent probes, such as FITC-labeled annexin V, is widely used for the detection of apoptotic cells, there are very limited probes that can be used in the near-infrared region (NIR) over 700 nm. Compared with visible light, NIR light is highly permeable in turbid biological samples and tissues. In addition, optical imaging in the NIR region shows low autofluorescence from biological samples, leading to clearer images with high signal to background ratios. Here, we report the synthesis of bioluminescence resonance energy transfer (BRET)-coupled annexin V-functionalized quantum dots (QDs) and their application to NIR optical detection of apoptotic cells.     

Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro

Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical fields, due to their characteristic large anti-Stokes shifts, narrow emission bands, deep tissue penetration and minimal background interference. UCNPs-derived multifunctional materials that integrate the merits of UCNPs and other functional entities have also attracted extensive attention. Here in this paper we present a core-shell structured nanomaterial, namely, NaGdF(4):Yb,Er@CaF(2)@SiO(2)-PS, which is multifunctional in the fields of photodynamic therapy (PDT), magnetic resonance imaging (MRI) and fluorescence/luminescence imaging. The NaGdF(4):Yb,Er@CaF(2) nanophosphors (10 nm in diameter) were prepared via sequential thermolysis, and mesoporous silica was coated as shell layer, in which photosensitizer (PS, hematoporphyrin and silicon phthalocyanine dihydroxide) was covalently grafted. The silica shell improved the dispersibility of hydrophobic PS molecules in aqueous environments, and the covalent linkage stably anchored the PS molecules in the silica shell. Under excitation at 980 nm, the as-fabricated nanomaterial gave luminescence bands at 550 nm and 660 nm. One luminescent peak could be used for fluorescence imaging and the other was suitable for the absorption of PS to generate singlet oxygen for killing cancer cells. The PDT performance was investigated using a singlet oxygen indicator, and was investigated in vitro in HeLa cells using a fluorescent probe. Meanwhile, the nanomaterial displayed low dark cytotoxicity and near-infrared (NIR) image in HeLa cells. Further, benefiting from the paramagnetic Gd(3+) ions in the core, the nanomaterial could be used as a contrast agent for magnetic resonance imaging (MRI). Compared with the clinical commercial contrast agent Gd-DTPA, the as-fabricated nanomaterial showed a comparable longitudinal relaxivities value (r(1)) and similar imaging effect.     

稀土上转光剂掺杂纳米TiO2催化可见光降解甲基紫

合成了一种新型含有稀土金属Er的上转光剂,此上转光剂在488nm可见光的激发下,可产生5个波长均小于387nm的上转换紫外发射峰。采用超声波分散的方法制备出了上转光剂掺杂的纳米TiO2,可见光光催化剂。实验结果表明,作为掺杂成分的上转光剂可有效地将可见光转化为紫外光并被纳米TiO2粉末吸收利用, 紫外光谱和离子色谱分析表明,在可见光照射16小时后甲基紫分解产物为Cl-和NO3-等,其降解率达92．2%, 大大高于未掺杂纳米TiO2的降解率71．2％。     

上转换/半导体核壳结构纳米复合材料光催化研究进展

上转换荧光材料具有将近红外光转换为紫外光和可见光的光学性能,与传统的半导体材料复合,使其光谱响应拓展到近红外区域,充分利用太阳光,从而提高光催化效率。核壳结构除能够有效地防止核(上转换纳米材料)被污染失活外,还可以使其紧密接触,有利于荧光共振能量的传递,提高壳(半导体材料)对光的利用率。系统论述了上转换半导体核壳结构纳米复合材料的制备方法、催化降解效率和催化影响因素,对此类复合材料的结合和催化机理进行分析,指出今后应加强高效率荧光材料和催化活性更强的半导体材料复合及如何在实际中应用的研究。     

Red Upconverter Nanocrystals Functionalized with Verteporfin for Photodynamic Therapy Triggered by Upconversion

Upconversion (UC) nanoparticles characterized by red upconversion emission, particularly interesting for biological applications, have been prepared and subsequently modified by the covalent anchoring of Verteporfin (Ver), an FDA approved photosensitizer (PS) which usually exerts its photodynamic activity upon excitation with red light. ZrO₂ was chosen as the platform where Yb³⁺ and Er³⁺ were inserted as the sensitizer and activator ions, respectively. Careful control of the doping ratio, along with a detailed physico-chemical characterization, was carried out. Upon functionalization with a silica shell to covalently anchor the photosensitizer, a theranostic nanoparticle was obtained whose architecture, thanks to a favorable energy level match and a uniform distribution of the PS, allowed us to trigger the photodynamic activity of Ver by upconversion, thus paving the way to the use of Photodynamic Therapy (PDT) in deep tissues, thanks to the higher penetrating power of NIR light.     

Construction of magnetic-targeted and NIR irradiation-controlled drug delivery platform with Fe3O4@Au@SiO2 nanospheres

Near-infrared (NIR) light has great potential in biomedical applications due to its advantages of deep penetration depth and low photodamage to biological tissues. In this paper, we constructed a novel core-shell structured drug nanocarrier, Fe₃O₄@Au@SiO₂, for the controlled delivery of etoposide (VP16), a chemotherapeutic drug for cancer patients. The novel core-shell structured drug delivery platform is composed of a mesoporous silica shell and a magnetic Fe₃O₄ core using Au nanoparticles (AuNPs) as the interlayer, which is characterized by atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, N₂ adsorption/desorption isotherms and the magnetic measurements with vibrating-sample magnetometer (VSM). The synergistic effects of AuNPs, mesoporous silica and Fe₃O₄ make the core-shell structured nanocomposites an excellent candidate for targeted and NIR light irradiation-controlled drug delivery. For the proposed nanocarrier of VP16, the mesopores in silica can enhance the encapsulation capacity of the nanocarrier and the AuNPs can effectively convert the NIR light into heat to speed up the drug deliver; meanwhile, the incorporation of Fe₃O₄ with high magnetization to the drug delivery platform realize drug targeting under an applied external magnetic field.     

Enhanced near-infrared to green upconversion from Er3+-doped oxyfluoride glass and glass ceramics containing BaGdF5 nanocrystals

In this work, effect of glass composition as well as ceramization on visible and near-infrared (NIR) luminescence properties along with their decay dynamics of Er³⁺ ions has been compared considering two different oxyfluoride glasses yielding BaF₂ and BaGdF₅ nanocrystals. Both the glass systems have exhibited an intense normal and upconversion green emission under ultraviolet (378 nm) and NIR (978 nm) excitations, respectively. A remarkable enhancement of these emission intensities is observed for gadolinium-(Gd) containing glasses. Interestingly, NIR fluorescence intensity from Er³⁺ ions at 1540 nm has showed marginal decrease in gadolinium-containing glass which is attributed to occurrence of strong excited-state absorption (ESA) due to higher fluorine content ensuing an augmentation of upconversion green emission with a concomitant decrease in NIR emission. The quadratic dependence of upconversion green emission intensity on its pump power for all the samples revealed biphotonic absorption process from ground-state ⁴I_15/2 to the excited-state ⁴I_11/2 followed by ESA of second photon to the ⁴F_7/2 level. The intense green upconversion emission as well as enhanced NIR fluorescence lifetimes indicate the suitability of these glass/glass ceramics for upconversion lasers and amplification in the third telecom window.     

花菁类近红外荧光探针在生物检测中的应用研究进展

随着现代生物学和生物技术的发展,近红外荧光探针作为一种重要的技术手段在许多领域都展现出了重要的应用价值。因具有背景干扰低、细胞损伤小、样品穿透性强、检测灵敏度高等优点,经常用于分子识别、医学诊断、生物分子检测以及生物成像等方面。本综述从金属离子检测、含硫小分子检测、活性氧（ROS）/活性氮（RNS）检测、酶识别、肿瘤细胞识别及治疗以及细胞内pH响应等方面,介绍了近年来花菁类荧光探针在生物检测中的应用研究进展。同时指出了花菁类荧光探针亟待解决的问题,通过花菁母体的结构修饰和改造提高探针的光稳定性、灵敏度、靶向性和水溶性,有望使其在生物检测以及疾病的诊断方面得到进一步应用发展。     

A sensitive and selective near-infrared fluorescent probe for mercuric ions and its biological imaging applications

A new mercury(II) near-infrared region fluorescent probe 3,9-dithia-6-monoazaundecane-tricarbocyanine has been designed and synthesized. It consists of two functional moieties: the tricarbocyanine performs as the near-infrared region fluorophore, and the 3,9-dithia-6-monoazaundecane acts as the selected binding site for metal ions. The near-IR excitation and emission profiles of the probe can minimize cell and tissue damage and avoid native fluorescence from natural cellular species. It exhibits fluorescence increase upon the binding of the Hg(2+) based on the inhibition of the photoinduced electron transfer quenching mechanism. Excellent sensitivity and selectivity for mercuric ions are observed with this probe. The value of the system is demonstrated by its use in monitoring the real-time uptake of Hg(2+) within HepG2 cells and five day old zebrafish. The synthesis and remarkable properties of it help to extend the development of metal ions fluorescent probes for biological applications.     

氟离子荧光探针的研究进展

氟离子是电负性最强、离子半径最小的阴离子,是一个强路易斯碱,在化学、生物学、医学和军事等方面都具有重要作用。适量的氟化物摄入人体可以预防龋齿、治疗骨质疏松症,但是过量的摄入会导致氟斑牙、氟骨症、尿石症以及癌症等疾病,因此氟离子的识别与检测具有重要意义。化学荧光探针具有选择性好、灵敏度高、方便快捷、成本低廉等优点,近年来化学研究者设计合成了大量的氟离子荧光探针。根据识别机理不同,氟离子荧光探针主要划分为3种:氢键型、路易斯酸受体型、氢键和路易斯酸混合型。综述了近年来不同类型的氟离子荧光探针的研究进展,总结了氢键型和路易斯酸型氟离子荧光探针的优缺点,对未来氟离子荧光探针的研究方向进行了展望。     

Cerium fluoride nanoparticles as a theranostic material for optical imaging of vulnerable atherosclerosis plaques

Atherosclerosis (AS) is a chronic progressive vascular disease, which can bring on a threat against the health. The eruption of unstable arteriosclerosis plaques has been linked to heart attacks and strokes. The accumulation of foamy macrophages initiates and evolves atherosclerotic plaques, which can be a good target for identifying vulnerable plaques. CD36 and OPN overexpress in foamy macrophages surface, which have a preferable relation with plaque disruption. Furthermore, we choose Yb ions and Tm ions as doping ions and Ce fluoride as matrix of luminescent materials and prepare upconversion luminescent nanoparticles. With the modification of CD36 antibody and OPN antibody, this material can target macrophages in arteriosclerosis plaques. As-prepared nanoparticles (CeF₃:Yb,Tm@SiO₂–CD36/OPN) can be excited by near-infrared light with deep tissue penetration, while emitting strong blue light to image arteriosclerosis plaques. In brief, this study provides a new upconversion luminescent material for the identification and detection of vulnerable atherosclerosis plaques.     

Fluorescent,Recombinant-Protein-Conjugated,Near-Infrared-Emitting Quantum Dots for in Vitro and in Vivo Dual-Color Molecular Imaging

Near-infrared (NIR)-emitting fluorescent probes are widely used for molecular imaging at the whole-body level. However, NIR-emitting fluorescent probes emitting over λ=700 nm are not suitable for molecular imaging at the cellular level, because most of the conventional fluorescence microscopes have very low optical sensitivity in the NIR region. Thus, to achieve fluorescence imaging at the cellular and whole-body levels by using single probes, visible and NIR-emitting dual-color fluorescent probes are desirable. For dual-color fluorescence molecular imaging, we synthesized fluorescent, recombinant-protein-conjugated, NIR-emitting quantum dots (QDs), in which the recombinant protein consists of enhanced green fluorescent protein (EGFP) and the immunoglobulin binding domain (B1) of protein G. This dual-color fluorescent QD probe binds the Fc region of immunoglobulin G (IgG) through its B1 domain at the QD surface and acts as a molecular-imaging probe at both the cellular and whole-body levels. In this paper, we present the synthesis of fluorescent, recombinant protein (HisEGFP-GB1)-conjugated, NIR-emitting QDs and their application to the dual-color molecular imaging of breast cancer cells in vitro and in vivo.     

Metal-based turn-on fluorescent probes for sensing nitric oxide

Nitric oxide, a reactive free radical, regulates a variety of biological processes. The absence of tools to detect NO directly, rapidly, specifically, and selectively motivated us to synthesize metal-based fluorescent probes to visualize the presence of NO. We prepared and investigated Co(II), Fe(II), Ru(II), Rh(II), and Cu(II) complexes as turn-on fluorescent NO sensors. Our exploration has provided insight into how the interaction of transition-metal centers with nitric oxide can be utilized for NO sensing.     

Effect of Ce dopant on upconversion and temperature sensing performances in homogeneous ultrasmall Y2O3:Yb3+/Ho3+ nanoparticles through flame aerosol synthesis

Flame aerosol synthesis (FAS) is an excellent strategy for continuous, fast, and mass production of small-size upconversion nanoparticles (UCNPs), which have high potential applications in fields like biological imaging, colour display and optical temperature sensing. However, flame-made UCNPs have received less attention, and relevant studies are limited. Herein, for the first time, we successfully fabricated cerium (Ce)-doped homogeneous ultrasmall Y₂O₃:Yb³⁺/Ho³⁺ UCNPs using a liquid-fed FAS method. Ce was doped to improve the upconversion luminescence (UCL) of the Y₂O₃:Yb³⁺/Ho³⁺ UCNPs. The overall UCL intensity was enhanced ～77.9-fold for an optimal concentration of 20 mol% Ce-doped UCNPs, compared with the UCNPs without Ce doping with a relatively homogeneous ultrasmall size of 8–10 nm. Further studies confirmed that both trivalent (Ce³⁺) and tetravalent (Ce⁴⁺) simultaneously exist in the Y₂O₃ hosts and are critical in enhancing the UCL properties. In addition, the fluorescence intensity ratio (FIR) method was used to evaluate the thermal properties of the fabricated UCNPs. Ce doping significantly improved the thermal sensitivity of Y₂O₃:Yb³⁺/Ho³⁺ UCNPs. An excellent relative sensitivity (S_R) of 0.622% K^?1 at 598 K was obtained for flame-made UCNPs doped with 20 mol% Ce.