NIR‐Triggered Release of Nitric Oxide with Upconversion Nanoparticles Inhibits Platelet Aggregation in Blood Samples

There is a great challenge to overcome the limitation of tissue penetration depth, while maximizing the benefit of light‐triggered biochemical cascades in a well‐defined mode simultaneously. Here, a new method of near‐infrared (NIR) light‐triggered release of nitric oxide (NO) by developing upconversion nanoparticles (UCNPs)‐based conjugate chemistry is reported. As the key nanotransducer in the design, core–shell‐structured UCNPs are encapsulated with a layer of SiO₂ and then covalently linked with a potent NO‐releasing donor (S‐nitroso‐N‐acetyl‐dl ‐penicillamine, SNAP). It is featured with highly localized breakage of chemical bonds of SNAP molecules by NIR–UV upconversion, enabling simultaneous NO release in a light dosage‐dependent manner. The biological effects of NO releasing are demonstrated by cellular imaging and inhibition of platelet aggregation from blood samples. This work provides a flexible and robust platform to generate cell‐signaling gas molecules trigged by NIR laser with deep tissue penetration.     

A Multifunctional Nanocrystalline CaF2:Tm,Yb@mSiO2 System for Dual‐Triggered and Optically Monitored Doxorubicin Delivery

Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli‐responsive drug delivery systems. Here, a nanoparticle system, CaF₂:Tm,Yb@mSiO₂, made of a mesoporous silica (mSiO₂) nanosphere with CaF₂:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface‐modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF₂:Tm,Yb@mSiO₂ enables us to trigger the drug release by two mechanisms. One is the pH‐triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)‐triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual‐triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.     

Highly Bright and Photostable Li(Gd,Y)F4:Yb,Er/LiGdF4 Core/Shell Upconversion Nanophosphors for Bioimaging Applications

Intense green‐emitting Li(Gd,Y)F₄:Yb,Er/LiGdF₄ core/shell (C/S) upconversion nanophosphors (UCNPs) with a tetragonal bipyramidal morphology are synthesized. The morphology and UC luminescence of the Li(Gd,Y)F₄:Yb,Er UCNPs are significantly affected by the Li precursors, and bright UC green‐emitting Li(Gd,Y)F₄:Yb,Er UCNPs with a tetragonal bipyramidal shape, i.e., UC tetragonal bipyramids (UCTBs), are synthesized using LiOH·H₂O as a Li precursor. A LiGdF₄ shell is grown on the Li(Gd,Y)F₄:Yb,Er UCTBs, and the C/S UCNPs exhibit 4.7 times higher luminescence intensity than core UCTBs. The C/S UCNPs show a high absolute UC quantum yield of 4.6% under excitation with 980 nm near infrared (NIR) light, and the UC luminescence from the C/S UCNPs is stable under continuous irradiation with the 980 nm NIR laser for 1 h. The hydrophobic surfaces of the as‐synthesized C/S UCNPs are modified to hydrophilic surfaces by using poly(acrylic acid) (PAA) for bioimaging applications. They are applied to human cervical adenocarcinoma (HeLa) cell imaging and SK‐MEL‐2 melanoma cell imaging and in vivo imaging, including subcutaneous and intramuscular imaging, and UC luminescence images with high signal‐to‐noise ratio are obtained. Furthermore, sentinel‐lymph‐node imaging is successfully conducted with the PAA‐capped Li(Gd,Y)F₄:Yb,Er/LiGdF₄ C/S UCNPs under illumination with NIR light.     

Upconverting nanoparticles for pre‐clinical diffuse optical imaging,microscopy and sensing: Current trends and future challenges

Upconverting nanoparticles (UCNPs) are a class of recently developed luminescent biomarkers that – in several aspects – are superior to organic dyes and quantum dots. UCNPs can emit spectrally narrow anti‐Stokes shifted light with quantum yields which greatly exceed those of two‐photon dyes for fluence rates relevant for deep tissue imaging. Compared with conventionally used Stokes‐shifting fluorophores, UCNP‐based imaging systems can acquire completely autofluorescence‐free data with superb contrast. For diffuse optical imaging, the multi‐photon process involved in the upconversion process can be used to obtain images with unprecedented resolution. These unique properties make UCNPs extremely attractive in the field of biophotonics. UCNPs have already been applied in microscopy, small‐animal imaging, multi‐modal imaging, highly sensitive bioassays, temperature sensing and photodynamic therapy. In this review, the current state‐of‐the‐art UCNPs and their applications for diffuse imaging, microscopy and sensing targeted towards solving essential biological issues are discussed.     

基于近红外上转换荧光共振能量传递体系的均相免疫分析

在上转换纳米晶(UCNPs)为供体的荧光共振能量传递(FRET)生物均相检测体系中,弱的供体光强度使FRET信号难于检测,同时还有来自生物基质的自发荧光干扰。这使得UCNPs不产生背景荧光和散射光的优点不能够充分地体现。针对这个问题,作者利用在800nm处有强近红外光的NaYF4:Yb3+,Tm3+UCNPs作为供体,在784nm处有表面等离子共振吸收带的金纳米粒子(GNPs)作为受体构建了新型的FRET体系。UCNPs偶联抗体(goat antihumanIgG)及GNPs偶联抗原(humanIgG),在抗原抗体免疫亲和作用下两者距离靠近;UCNPs荧光光谱和GNPs吸收光谱有效交叠,使FRET发生。当体系中加入单纯humanIgG,竞争性地争夺与goatantihumanIgG结合位点,破坏FRET构建,供体近红外光增强。根据此对应关系,确定humanIgG检测限为5μg·mL-1。这种方法可适用于更广泛的荧光分析。     

Red/Near‐Infrared Emissive Metalloporphyrin‐Based Nanodots for Magnetic Resonance Imaging‐Guided Photodynamic Therapy In Vivo

Near‐infrared emissive (NIR) porphyrin‐implanted carbon nanodots (PCNDs or MPCNDs) are prepared by selectively carbonization of free base or metal complexes [M = Zn(II) or Mn(III)] of tetra‐(meso‐aminophenyl)porphyrin in the presence of citric acid. The as‐prepared nanodots exhibit spontaneously NIR emission, small size, good aqueous dispersibility, and favorable biocompatibility characteristic of both porphyrins and pristine carbon nanodots. The subcellular localization experiment of nanodots indicates a lysosome‐targeting feature. And the in vitro photodynamic therapy (PDT) results on HeLa cells indicate the nanodots alone have no adverse effect on tumor cells, but display remarkable photodynamic efficacy upon irradiation. Moreover, MnPCNDs containing paramagnetic Mn(III) ions, which possesses good biocompatibility, NIR luminescence, and magnetic resonance imaging and efficient singlet oxygen production, are further studied in magnetic resonance imaging‐guided photodynamic therapy in vivo.     

Dye‐Sensitized Core/Shell Upconversion Nanoparticles for Detecting Nitrites in Plant Cells

A fluorescent nanoprobe is reported for rapid detection of nitrites (NO₂^?) in plant cells. The probe is fabricated by linking neutral reds (NR) to the surface of upconversion fluorescent core/shell nanocrystalline with the bridging of polyethylene glycol (PEG) molecules. The fluorescence of upconversion nanoparticles (UCNPs) is stored by NR through fluorescence resonance energy transfer (FRET) under 980 nm excitation that can be released by further linking to NO₂^?. It is observed that the intensity rate of green to red emission of NR‐modified UCNPs changes linearly with increasing the amount of NO₂^?. So that concentration of NO₂^? can be accordingly addressed. Worth mentioning is that, comparing with bare core upconversion nanoparticles (NPs), core/shell UCNPs can greatly reduce the surface quenching of the fluorescence induced by solvents instead of NR and thus leading to the enhancement of signal‐to‐noise ratios. Moreover, excitation of core/shell UCNPs requires only a much lower power (0.06 W cm^?2) than bare cores which is beneficial to reducing the decomposition of NR to stabilize the FRET processes. Under the optimum conditions, the detection limit of nitrite in plant cells was 0.1 µg mL^?1.     

Water‐Soluble Monolayer Molybdenum Disulfide Quantum Dots with Upconversion Fluorescence

Uniform water‐soluble monolayer MoS₂ quantum dots (MQDs) with lateral sizes of ≈2.1 nm, a clearly zigzag‐terminated edge, and a hexagonal lattice structure are achieved using ammonium molybdate, thiourea, and N‐acetyl‐l ‐cysteine (NAC) as precursors and the capping reagent in a facile one‐pot hydrothermal approach. MQDs have good dispersity and high stability in aqueous suspension and exhibit a significantly larger direct bandgap (3.96 eV) compared to monolayer MoS₂ nanosheets (1.89 eV). Pronounced blue‐shifts in the wavelengths of both the excitonic absorption and intrinsic state emission with activated strong luminescence at room temperature beyond monolayer MoS₂ nanosheets is demonstrated. Unusual upconversion photoluminescence is also observed and is caused by two successive transfers of energy from the near‐infrared (NIR) absorption generated by the NAC capping reagent to the hexagonal structure of MQDs. Additional optical properties of MQDs may provide numerous exciting technological applications. Here, MQDs are demonstrated as a highly selective fluorescent reagent for detecting tetracycline hydrochloride under UV and NIR irradiation.     

上转换纳米晶标记适配子的新型光开关

适配子是对靶分子有高特异性和亲合力的单链寡核苷酸.由于其结构特性,常用于生物检测.目前的适配子光传感器多采用染料或量子点为标记物,存在背景高,不稳定等缺点.新型的荧光材料上转换纳米晶(UCNPs)因其特殊的发光性质颇受关注.与传统的下转换材料相比,它是近红外光激发,避免产生背景荧光和杂散光.利用聚乙酰亚胺为表面配体,水...     

Construction of a Dual Drug Carrier on the Basis of Hollow Structured Upconversion Nanoparticles for pH‐Responsive Drug Delivery and UCL/MRI Dual Mode Imaging

A series of Gd³⁺ doping hollow upconversion nanoparticles NaYF₄:Yb,Gd,Tm (h‐UNCP) are prepared successfully. The hollow NaYF₄:Yb,Gd,Tm possess excellent upconversion luminescence (UCL) and large longitudinal relativity (r₁ = 128.3 mm ^?1 s^?1), which can be potentially used for UCL/magnetic resonance imaging (MRI) dual mode imaging. On the basis of the optimal h‐UCNP, doxorubicin hydrochloride (DOX) and methotrexate (MTX) are used as drug models to prepare a dual drug carrier. After the encapsulation of DOX on the h‐UCNP, chitosan (CS) is further wrapped and then used to load MTX to obtain a dual drug carrier h‐UCNPs/DOX/CS/MTX. The pH responsive release of DOX and MTX is discussed. The MTX release climbs from 33% to 100% by regulating the pH from 5.8 to 7.4. The DOX release is different at different pH conditions. The synergistic effect of DOX and MTX on the cancer cells is confirmed by cell viability. The h‐UCNPs/DOX/CS/MTX are tracked by cells UCL imaging and vivo MRI imaging. The excellent performance of UCL imaging and positive MRI images demonstrates that h‐UCNPs/DOX/CS/MTX can be used for UCL/MRI dual mode imaging. All the results show the potential application of h‐UCNPs/DOX/CS/MTX in pH responsive release and UCL/MRI dual imaging.     

Colour tunability in a bimodal fluorescent hybrid nanostructure UCNPs@AuNPs@QDs

In the present work, lysine modified NaY_0.78Er_0.02Yb_0.2F₄ upconversion nanoparticles (UCNPs, positively charged) and lysine modified ZnSe:Mn²⁺ quantum dots (QDs, positively charged) are attached onto the surface of citrate reduced gold nanoparticles (AuNPs, negatively charged). The gold nanoparticles not only entangle the QDs and the UCNPs, through electrostatic interaction, but also tune the optical properties of UCNPs through the effect of surface plasmon resonance. The hybrid nanostructure gives green emission both through photoluminescence (under UV excitation) and through photon upconversion (under IR light excitation) process. The colour tuning is observed through variation in the size of QDs and through plasmonic effect of gold nanoparticles. In both the cases, the colour of emission gradually changes from green to red. The colour tunability and bi-modal photon conversion property of this material could be useful for its application in the field of bio-imaging and solar energy harvesting.     

Tens of thousands‐fold upconversion luminescence enhancement induced by a single gold nanorod

Upconversion nanoparticles (UCNPs) have gained increasing attention for their wide applications in bioimaging, displays and photovoltaics. However, low efficiency has been an ongoing challenge for further developments. In this work, it is proposed that the ultrasmall size of UCNPs is essential for achieving large enhancement factors and experimentally demonstrated with 4‐nm UCNPs. A strategy of plasmonic dual resonance is proposed in which two distinct localized surface plasmon resonance (LSPR) peaks of gold nanorods (GNRs) were designed to perfectly match both the excitation and emission light wavelength of UCNPs. Combining the excitation enhancement and Purcell effect, a huge enhancement factor of tens of thousands‐fold is stochastically demonstrated for single UCNPs in solution. The largest overall enhancement region is close to the end of a GNR but not in its central part. The excitation enhancement (up to three orders of magnitude) and the emission enhancement (larger than one order of magnitude) induced by the Purcell effect are experimentally demonstrated separately. This study provides insight into how to achieve a very large upconversion enhancement factor with surface plasmons and will catalyze development of UCNPs’ extensive applications.

     

Core–Shell Bi2Se3@mSiO2‐PEG as a Multifunctional Drug‐Delivery Nanoplatform for Synergistic Thermo‐Chemotherapy with Infrared Thermal Imaging of Cancer Cells

Thermo‐chemotherapy combining photothermal therapy (PTT) with chemotherapy has become a potent approach for antitumor treatment. In this study, a multifunctional drug‐delivery nanoplatform based on polyethylene glycol (PEG)‐modified mesoporous silica‐coated bismuth selenide nanoparticles (referred to as Bi₂Se₃@mSiO₂‐PEG NPs) is developed for synergistic PTT and chemotherapy with infrared thermal (IRT) imaging of cancer cells. The product shows no/low cytotoxicity, strong near‐infrared (NIR) optical absorption, high photothermal conversion capacity, and stability. Utilizing the prominent photothermal effect, high‐contrast IRT imaging and efficient photothermal killing effect on cancer cells are achieved upon NIR laser irradiation. Moreover, the successful mesoporous silica coating of the Bi₂Se₃@mSiO₂‐PEG NPs cannot only largely improve the stability but also endow the NPs high drug loading capacity. As a proof‐of‐concept model, doxorubicin (DOX) is successfully loaded into the NPs with rather high loading capacity (≈50.0%) via the nanoprecipitation method. It is found that the DOX‐loaded NPs exhibit a bimodal on‐demand pH‐ and NIR‐responsive drug release property, and can realize effective intracellular drug delivery for chemotherapy. The synergistic thermo‐chemotherapy results in a significantly higher antitumor efficacy than either PTT or chemotherapy alone. The work reveals the great potential of such core–shell NPs as a multifunctional drug‐delivery nanosystem for thermo‐chemotherapy.     

Er~(3+),Yb~(3+)共掺杂Y_2O_3纳米晶体粉末中1.5μm近红外发光增强现象的研究

用燃烧法制备了平均粒径为10和40nm的(Y0.96Er0.02Yb0.02)O3纳米晶体样品,并通过1200℃高温退火获得了同样组分的体材料样品。利用X射线衍射谱(XRD),傅里叶变换红外吸收光谱(FTIR),透射电镜(TEM)和透射电镜(SEM)照片对样品的晶体结构和形貌进行了表征。测量了不同样品980nm激发下的上转换发射光谱和近红外发射光谱。对实验结果的分析发现,随着粒径的减小,样品发射光谱中红光和近红外发射的成分增加。产生这一现象的原因是由于纳米材料具有比表面积大的特点,能够吸附更多的OH-(振动能量3200～3800cm-1),OH-数量的增加使电子从Er3+的4I11/2→4I13/2能级(能量差3600cm-1)的无辐射弛豫速率增大,这一无辐射弛豫过程减少了4I11/2上的电子布居数,使绿光发射减弱;同时增加了4I13/2上的电子布居数,使红光和近红外发射增强。40nm样品的1.5μm发射主峰强度是体材料的1.6倍,这一结果对纳米发光材料的实际应用是很有意义的。     

水溶性NaYF_4∶Yb/Tm纳米粒子的制备及其上转换发光性质

利用溶剂热法合成了NaYF4:20%Yb,0.5%Tm上转换发光纳米粒子(UCNPs),用扫描电子显微镜、X射线衍射分析、发光光谱测量等手段对水溶性纳米颗粒进行了形貌和发光性质表征。结果表明,UCNPs是纯立方相的NaYF4,尺寸均匀分布在30nm左右。在980nm红外光的激发下,UCNPs能够发出肉眼可见的明亮的蓝紫色光。发射光谱中最强发射峰在479nm,来源于Tm3+离子的1G4→3H6发射,并且给出了UCNPs的上转换发光机制。利用聚乙烯吡咯烷酮(PVP)作为表面活性剂所制备的上转换发光纳米颗粒具有良好的水溶性,尺寸较小,在生物荧光标记领域具有潜在的应用价值。     

Enhancement of the 808 nm Photothermal Effect of Gold Nanorods by Thiol‐Induced Self‐Assembly

Gold (Au) nanomaterials are promising photothermal agents for the selective treatment of tumor cells owing to the strong capability to convert near‐infrared (NIR) irradiation into heat energy. One basic issue for practical photothermal therapy is the enhancement of photothermal effect in NIR region. Here, various low‐molecular‐weight thiols are applied to induce one‐dimensional (1D) self‐assembly of Au nanorods (NRs), which leads to the redshift of absorption peak towards NIR region. As a result, the 1D assembled Au NRs exhibit improved photothermal effect at 808 nm in comparison to unassembled Au NRs.     

Long‐Term Colloidal and Chemical Stability in Aqueous Media of NaYF4‐Type Upconversion Nanoparticles Modified by Ligand‐Exchange

Surface capping is an essential component of nanoparticles as it provides access to their outstanding properties in the real world. Upconversion nanoparticles are predominantly interesting for use in biological environments, due to their excellent optical properties such as the conversion of near‐infrared excitation light into emissions in the visible or UV range of the spectrum, high photostability, and the absence of any intermittence. One of the most efficient upconversion nanoparticles, consisting of lanthanide doped NaYF₄, suffers from limited stability in aqueous media. This study investigates a set of five types of surface coatings, ranging from small ligands to polymers of different charge and different coordinating groups, on monodisperse 28 ± 0.9 nm sized NaYF₄(Yb,Er) nanoparticles modified by a two‐step ligand exchange mediated by NOBF₄. Information on the long‐term chemical and colloidal stability for highly diluted aqueous dispersions of these particles is acquired by transmission electron microscopy, dynamic light scattering, and luminescence spectroscopy. The findings are of importance for the development of probes and labels based on upconversion nanoparticles for biological applications.     

Targeting Upconversion Nanoprobes for Magnetic Resonance Imaging of Early Colon Cancer

Colon cancer (CC) is one of the most common intestinal malignancies and is difficult to detect in its early stage by magnetic resonance imaging (MRI) with currently used contrast agents (CAs). The development of targeted CAs contributes to the early diagnosis of CC and thereby enables early intervention and timely therapy. Considering the outstanding performance of upconversion nanoprobes (UCNPs) in high‐performance MR and fluorescence imaging, a new type of nanoprobes with considerably enhanced imaging performance is developed herein. Carcinoembryonic antigen (CEA) antibody is conjugated onto the surface of UCNPs to achieve the targeted imaging of early CC tumors, which overexpress CEA. Both toxicity tests and histological/hematological examinations demonstrate the excellent biocompatibility of these CC‐targeting nanoprobes, which possess great potential for clinical application in the early diagnosis of CC.     

红外辐射材料的制备与光谱研究

本文开展了红外辐射材料ＺｒＯ２、Ａｌ２Ｏ３及其复合氧化物ＺｒＯ２－Ａｌ２Ｏ３的纳米材料制备方法研究,对其开展了ＦＴＩＲ,ＮＩＲ ＦＴ－Ｒａｍａｎ、ＸＲＤ和红外发射光谱研究,研究表明复合氧化物具有较好的红外发射性能。在构效关系的研究基础上,探讨其实际应用价值。     

Enhanced Photoelectric and Photothermal Responses on Silicon Platform by Plasmonic Absorber and Omni‐Schottky Junction

Recent progresses in plasmon‐induced hot electrons open up the possibility to achieve photon harvesting beyond the fundamental limit imposed by band‐to‐band transitions in semiconductors. To obtain high efficiency, both the optical absorption and electron emission/collection are crucial factors that need to be addressed in the design of hot electron devices. Here, we demonstrate a photoresponse as high as 3.3mA/W at 1500nm on a silicon platform by plasmonic absorber (PA) and omni‐Schottky junction integrated photodetector, reverse biased at 5V and illuminated with 10mW. The PA fabricated on silicon consists of a monolayer of random Au nanoparticles (NPs), a wide‐band gap semiconductor (TiO₂) and an optically thick Au electrode, resulting in broadband near‐infrared (NIR) absorption and efficient hot‐electron transfer via an all‐around Schottky emission path. Meanwhile, time and spectral‐resolved photoresponse measurements reveal that embedded NPs with superior absorption resembling plasmonic local heating sources can transfer their energy to electricity via the photothermal mechanism, which until now has not been adequately assessed or rigorously differentiated from the photoelectric process in plasmon‐mediated photon harvesting nano‐systems.