Enhanced red emission from GdF3:Yb3+,Er3+ upconversion nanocrystals by Li+ doping and their application for bioimaging

Under 980?nm near-infrared (NIR) excitation, upconversion luminescent (UCL) emission of GdF(3):Yb,Er upconversion nanoparticles (UCNPs) synthesized by a simple and green hydrothermal process can be tuned from yellow to red by varying the concentration of dopant Li(+) ions. A possible mechanism for enhanced red upconverted radiation is proposed. A layer of silica was coated onto the surface of GdF(3):Yb,Er,Li UCNPs to improve their biocompatibility. The silica-coated GdF(3):Yb,Er,Li UCNPs show great advantages in cell labeling and in vivo optical imaging. Moreover, GdF(3) UCNPs also exhibited a positive contrast effect in T(1)-weighted magnetic resonance imaging (MRI). These results suggest that the GdF(3) UCNPs could act as dual-modality biolabels for optical imaging and MRI.     

Multifunctional Core–Shell Structured Nanocarriers for Synchronous Tumor Diagnosis and Treatment In Vivo

Multifunctional, mesoporous, silica‐coated upconversion luminescent/magnetic NaGdF₄:Yb/Er@NaGdF₄:Yb@mSiO₂? PEG (referred to as UCNPS; PEG=polyethylene glycol) nanocomposites were fabricated through a phase‐transfer‐assisted surfactant‐templating coating process, followed by hydrophilic polymer (PEG) functionalization to improve the stability and biocompatibility. The UCNP core imparts the nanomaterials with luminescence and magnetic properties for simultaneous upconversion optical and magnetic resonance (MR) imaging, whereas the mesoporous shell affords the nanomaterials the ability to load the anticancer drug doxorubicin. Proof‐of‐principle in vitro and in vivo experiments are presented to demonstrate that the resultant composite nanomaterials can serve as nanotheranostics for synchronous upconversion luminescence/MR dual modal imaging and anticancer drug delivery; this finally realizes the integration of diagnostics and the treatment of cancers.     

Upconversion nanoparticle-based fluorescence resonance energy transfer assay for Cr(III) ions in urine

A novel assay of chromium(III) ion based on upconversion fluorescence resonance energy transfer was designed and established. Lysine-capped NaYF₄:Yb/Er upconversion nanoparticles (UCNPs) and dimercaptosuccinic acid-capped gold nanoparticles (AuNPs) were used as the energy donor and acceptor, respectively. They were bound together via electrostatic interaction, resulting in the quenching of the fluorescence of UCNPs by AuNPs. Chromium(III) ions can specifically and strongly interact with dimercaptosuccinic acid that was modified on the surface of AuNPs, leading to the separation of AuNPs from UCNPs and the recovery of fluorescence of UCNPs. The fluorescence recovery of UCNPs showed a good linear response to Cr³⁺ concentration in the range of 2–500 nM with a detection limit of 0.8 nM. This method was further applied to determine the levels of Cr³⁺ in urine. Compared with other fluorescence methods, current method displayed very high sensitivity and signal-to-noise ratio because of the excitation of near-infrared that can eliminate autofluorescence, providing a promising examination of biological samples for the diagnostic purposes.     

Upconversion nanophosphors for small-animal imaging

Rare-earth upconversion nanophosphors (UCNPs), when excited by continuous-wave near-infrared light, exhibit a unique narrow photoluminescence with higher energy. Such special upconversion luminescence makes UCNPs promising as bioimaging probes with attractive features, such as no auto-fluorescence from biological samples and a large penetration depth. As a result, UCNPs have emerged as novel imaging agents for small animals. In this critical review, recent reports regarding the synthesis of water-soluble UCNPs and their surface modification and bioconjugation chemistry are summarized. The applications of UCNPs for small-animal imaging, including tumor-targeted imaging, lymphatic imaging, vascular imaging and cell tracking are reviewed in detail. The exploration of UCNPs as multifunctional nanoscale carriers for integrated imaging and therapy is also presented. The biodistribution and toxicology of UCNPs are further described. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for small-animal imaging (276 references).     

Dual latex/surfactant templating of hollow spherical silica particles with ordered mesoporous shells

Hollow spherical silica particles with hexagonally ordered mesoporous shells are synthesized with the dual use of cetyltrimethylammonium bromide (CTAB) and unmodified polystyrene latex microspheres as templates in concentrated aqueous ammonia. In most of the hollow mesoporous particles, cylindrical pores run parallel to the hollow core due to interactions of CTAB/silica aggregates with the latices. Effects on the product structure of the CTAB:latex ratio, the amount of aqueous ammonia, and the latex size are studied. Hollow particles with hexagonally patterned mesoporous shells are obtained at moderate CTAB:latex ratios. Too little CTAB causes silica shell growth without surfactant templating, and too much induces nucleation of new mesoporous silica particles without latex cores. The concentration of ammonia must be large to induce co-assembly of CTAB, silica, and latex into dispersed particles. The results are consistent with the formation of particles by addition of CTAB/silica aggregates to the surface of latex microspheres. When the size and number density of the latex microspheres are changed, the size of the hollow core and the shell thickness can be controlled. However, if the microspheres are too small (50 nm in this case), agglomerated particles with many hollow voids are obtained, most likely due to colloidal instability.     

X‐ray Radiation‐Controlled NO‐Release for On‐Demand Depth‐Independent Hypoxic Radiosensitization

Multifunctional stimuli‐responsive nanotheranostic systems are highly desirable for realizing simultaneous biomedical imaging and on‐demand therapy with minimized adverse effects. Herein, we present the construction of an intelligent X‐ray‐controlled NO‐releasing upconversion nanotheranostic system (termed as PEG‐USMSs‐SNO) by engineering UCNPs with S‐nitrosothiol (R‐SNO)‐grafted mesoporous silica. The PEG‐USMSs‐SNO is designed to respond sensitively to X‐ray radiation for breaking down the S N bond of SNO to release NO, which leads to X‐ray dose‐controlled NO release for on‐demand hypoxic radiosensitization besides upconversion luminescent imaging through UCNPs in vitro and in vivo. Thanks to the high live‐body permeability of X‐ray, our developed PEG‐USMSs‐SNO may provide a new technique for achieving depth‐independent controlled NO release and positioned radiotherapy enhancement against deep‐seated solid tumors.     

Facile fabrication of hollow mesoporous silica nanospheres for superhydrophilic and visible/near-IR antireflection coatings

A series of hierarchically mesostructured silica nanoparticles (MSNs) less than 100 nm in size were fabricated by means of a one-step synthesis using dodecanethiol (C(12)-SH) and cetyltrimethylammonium bromide (CTAB) as the dual template, and trimethylbenzene (TMB) as the swelling agent. Silica nanoparticles with varied morphologies and structures, including mesoporous silica nanoparticles with tunable pore size, mesoporous silica nanoparticles with a thin solid shell, hollow mesoporous silica nanoparticles with tunable cavity size, and hollow mesoporous silica nanoparticles with a thin solid shell, were obtained by regulating the TMB/CTAB molar ratio and the stirring rate with the assistance of C(12)-SH. Silica particulate coatings were successfully fabricated by using MSNs with varied morphologies and structures as building block through layer-by-layer dip-coating on glass substrates. The thickness and roughness of the silica particulate coatings could be tailored by regulating the deposition cycles of nanoparticles. The silica particulate coatings composed of hollow mesoporous silica nanoparticles with a thin shell (S2) increased the maximum transmittance of slide glass from 90 to 96%, whereas they reduced its minimum reflection from 8 to 2% at the optimized wavelength region that could be adjusted from visible to near-IR with a growing number of deposition cycles. The coatings also exhibited excellent superhydrophilic and antifogging properties. These mesostructured silica nanoparticles are also expected to serve as ideal scaffolds for biological, medical, and catalytic applications.     

Multifunctional Nano‐Bioprobes Based on Rattle‐Structured Upconverting Luminescent Nanoparticles

Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in versatile bioapplications. For the first time, organosilica‐shelled β‐NaLuF₄:Gd/Yb/Er nanoprobes with a rattle structure have been designed for dual‐modal imaging and photodynamic therapy (PDT). Benefiting from the unique rattle structure and aromatic framework, these nanoprobes are endowed with a high loading capacity and the disaggregation effect of photosensitizers. After loading of β‐carboxyphthalocyanine zinc or rose Bengal into the nanoprobes, we achieved higher energy transfer efficiency from UCNPs to photosensitizers as compared to those with conventional core–shell structure or with pure‐silica shell, which facilitates a large production of singlet oxygen and thus an enhanced PDT efficacy. We demonstrated the use of these nanoprobes in proof‐of‐concept X‐ray computed tomography (CT) and UC imaging, thus revealing the great potential of this multifunctional material as an excellent nanoplatform for cancer theranostics.     

Facile synthesis of monodisperse microspheres and gigantic hollow shells of mesoporous silica in mixed water-ethanol solvents

Mesoporous silica materials with a variety of morphologies, such as monodisperse microspheres, gigantic hollow structures comprising a thin shell with a hole, and gigantic hollow structures consisting of an outer thin shell and an inner layer composed of many small spheres, have been readily synthesized in mixed water-ethanol solvents at room temperature using cetyltrimethylammonium bromide (CTAB) as the template. The obtained mesoporous silica generally shows a disordered mesostructure with typical average pore sizes ranging from 3.1 to 3.8 nm. The effects of the water-to-ethanol volume ratio (r), the volume content of tetraethyl orthosilicate TEOS (x), and the CTAB concentration in the solution on the final morphology of the mesoporous silica products have been investigated. The growth process of gigantic hollow shells of mesoporous silica through templating emulsion droplets of TEOS in mixed water-ethanol solution has been monitored directly with optical microscopy. Generally, the morphology of mesoporous silica can be regulated from microspheres through gigantic hollow structures composed of small spheres to gigantic hollow structures with a thin shell by increasing the water-to-ethanol volume ratio, increasing the TEOS volume content, or decreasing the CTAB concentration. A plausible mechanism for the morphological regulation of mesoporous silica by adjusting various experimental parameters has been put forward by considering the existing state of the unhydrolyzed and partially hydrolyzed TEOS in the synthesis system.     

Lanthanide‐Doped LiLuF4 Upconversion Nanoprobes for the Detection of Disease Biomarkers

Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in bioapplications. Exploring new host materials to realize efficient upconversion luminescence (UCL) output is a goal of general concern. Herein, we develop a unique strategy for the synthesis of novel LiLuF₄:Ln³⁺ core/shell UCNPs with typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er³⁺ and Tm³⁺, respectively. Based on our customized UCL biodetection system, we demonstrate for the first time the application of LiLuF₄:Ln³⁺ core/shell UCNPs as sensitive UCL bioprobes for the detection of an important disease marker β subunit of human chorionic gonadotropin (β‐hCG) with a detection limit of 3.8 ng mL⁻¹, which is comparable to the β‐hCG level in the serum of normal humans. Furthermore, we use these UCNPs in proof‐of‐concept computed tomography imaging and UCL imaging of cancer cells, thus revealing the great potential of LiLuF₄:Ln³⁺ UCNPs as efficient nano‐bioprobes in disease diagnosis.     

General Route to Multifunctional Uniform Yolk/Mesoporous Silica Shell Nanocapsules: A Platform for Simultaneous Cancer‐Targeted Imaging and Magnetically Guided Drug Delivery

Hollow mesoporous SiO₂ (mSiO₂) nanostructures with movable nanoparticles (NPs) as cores, so‐called yolk‐shell nanocapsules (NCs), have attracted great research interest. However, a highly efficient, simple and general way to produce yolk‐mSiO₂ shell NCs with tunable functional cores and shell compositions is still a great challenge. A facile, general and reproducible strategy has been developed for fabricating discrete, monodisperse and highly uniform yolk‐shell NCs under mild conditions, composed of mSiO₂ shells and diverse functional NP cores with different compositions and shapes. These NPs can be Fe₃O₄ NPs, gold nanorods (GNRs), and rare‐earth upconversion NRs, endowing the yolk‐mSiO₂ shell NCs with magnetic, plasmonic, and upconversion fluorescent properties. In addition, multifunctional yolk‐shell NCs with tunable interior hollow spaces and mSiO₂ shell thickness can be precisely controlled. More importantly, fluorescent‐magnetic‐biotargeting multifunctional polyethyleneimine (PEI)‐modified fluorescent Fe₃O₄@mSiO₂ yolk‐shell nanobioprobes as an example for simultaneous targeted fluorescence imaging and magnetically guided drug delivery to liver cancer cells is also demonstrated. This synthetic approach can be easily extended to the fabrication of multifunctional yolk@mSiO₂ shell nanostructures that encapsulate various functional movable NP cores, which construct a potential platform for the simultaneous targeted delivery of drug/gene/DNA/siRNA and bio‐imaging.     

Multifunctional Core–Shell Upconverting Nanoparticles for Imaging and Photodynamic Therapy of Liver Cancer Cells

Lanthanide‐doped upconversion nanoparticles (UCNPs) have attracted considerable attention for their application in biomedicine. Here, silica‐coated NaGdF₄:Yb,Er/NaGdF₄ nanoparticles with a tetrasubstituted carboxy aluminum phthalocyanine (AlC₄Pc) photosensitizer covalently incorporated inside the silica shells were prepared and applied in the photodynamic therapy (PDT) and magnetic resonance imaging (MRI) of cancer cells. These UCNP@SiO₂(AlC₄Pc) nanoparticles were uniform in size, stable against photosensitizer leaching, and highly efficient in photogenerating cytotoxic singlet oxygen under near‐infrared (NIR) light. In vitro studies indicated that these nanoparticles could effectively kill cancer cells upon NIR irradiation. Moreover, the nanoparticles also demonstrated good MR contrast, both in aqueous solution and inside cells. This is the first time that NaGdF₄:Yb,Er/NaGdF₄ upconversion‐nanocrystal‐based multifunctional nanomaterials have been synthesized and applied in PDT. Our results show that these multifunctional nanoparticles are very promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.     

General one-pot strategy to prepare multifunctional nanocomposites with hydrophilic colloidal nanoparticles core/mesoporous silica shell structure

A general and facile strategy was developed to coat hydrophilic inorganic nanoparticles directly with mesoporous silica nanoparticles (MSNs). The cationic surfactant of cetyltrimethylammonium bromide (CTAB) was adsorbed to various negatively charged CdTe quantum dots, Fe(3)O(4) nanocrystals or Au nanoparticles, introducing the bilayer of CTAB overcoating with positive charge. The subsequent sol-gel reaction of TEOS with the basic catalyst resulted in uniform nanocomposites. The concentration of CTAB and NH(4)OH in the recipe strongly influenced the number of inorganic nanoparticles in the nanocomposites and the homogeneity of MSNs shell. One dimensional Au nanorods and larger size of solid SiO(2) nanoparticles were also able to coat with MSNs using a similar synthetic procedure. The proposed method was greatly simplified without the help of any mediators or silane coupling agents and excellent mesostructural performance was readily achieved. Compared to the methods known from the literatures for the coating of hydrophobic nanoparticles, this efficient way is especially useful for trapping different hydrophilic nanoparticles with arbitrary sizes and shapes into MSNs. These highly versatile multifunctional nanocomposites, together with the pH-responsible drug release behaviors, non-toxicity to normal cells and ease of uptake into cancer cells, are expected to be utilized as drug delivery system for simultaneous imaging and therapeutic applications.     

Yb/Er掺杂Y2O3纳米核壳颗粒的荧光性能及体内标定研究

为改善无机Y2O3上转换纳米粒子(UCNPs)的荧光性能,且同步实现其在生物体内的成像标定,通过共沉淀法及梯度合成工艺,制备出各组不同壳层厚度的Y2O3:Yb³⁺,Er³⁺@Y2O3:Yb³⁺ UCNPs。利用透射电子显微镜(TEM)扫描、X射线衍射(XRD)、上转换荧光(UCL)光谱、UCL寿命等对样品的形貌、结构及荧光性能进行了表征。结果表明：利用共沉淀法制得小尺寸Y2O3:Yb³⁺,Er³⁺@Y2O3:Yb³⁺纳米核壳颗粒,平均粒径范围在25.57~26.24 nm之间。通过调整Yb³⁺浓度和水浴时间优化合成工艺,获得高发射强度、长荧光寿命方案(80% Yb掺杂,8 h水浴)。高红绿比的荧光发射特征,决定其在小动物体内荧光标定检测时更宜采用红色信道。     

掺杂比例和光敏剂对上转换纳米材料性能的影响

以NaYF_4材料为基质的上转换纳米颗粒(UCNPs)是最早报道的、应用范围最广的上转换材料之一。掺杂了稀土离子的颗粒不但可以在不同激发条件下发射出不同波长和强度的荧光,而且可以与多种光敏分子搭配使用,通过荧光共振能量转移产生单线态氧,实现生物医学成像或诊疗方面的应用。但是其形貌和荧光性能均受制备方法和工艺条件的影响较大。本文通过水热法合成了两类掺杂不同稀土离子的十种NaYF_4 UCNPs,在保持掺杂离子的终浓度不变的条件下,探究离子类型与比例对纳米材料的结构和上转换发光性能的影响。在此基础上,探索了多种卟啉类光敏剂分子与NaYF_4 UCNPs发生能量转换及单线态氧的产生能力。本工作可为基于NaYF_4材料的上转换颗粒的规模化制备和工艺升级提供数据支撑和理论参考。     

Fabricating UCNPs-AuNPs Fluorescent Probe for Sensitive Sensing Thiamphenicol

Anovel fluorescent probe has been constructed based on fluorescence resonance energy transfer(FRET) between upconversion nanomaterials(UCNPs) NaYF₄:Yb,Er and gold nanoparticles(AuNPs). The fluorescent "off-on" switching was formed for the detection of thiamphenicol(TAP) in egg samples. The fluorescence of UCNPs can be quenched to a certain degree by AuNPs. After adding TAP, the AuNPs generated aggregation and the fluorescence of UCNPs was recovered. The synthesized amination UCNPs and AuNPs were characterized by Fourier transform infrared spectroscopy(FTIR), UV-Vis, X-ray diffraction(XRD), energy dispersive spectrometer(EDS), and transmission electron microscope(TEM) techniques for observation and confirmation. As a model target, the detection of TAP has two linear ranges in the buffer solution within 0.01-0.1 μmol/L and 0.1-1 μmol/L using this fluorescent probe. The detection limit was obtained to be 0.003 μmol/L(S/N=3), which is favorable for trace analysis. The recovery of TAP from 98.2% to 105.3% was obtained, and the relative standard deviation(RSD) was from 2.5% to 4.3%. Furthermore, the method established in this study based on the UCNPs auto-low background fluorescence has high selectivity and strong ability to eliminate interference, which is beneficial to analyzing complex samples.     

具有协同表面配体的水溶性稀土上转换发光纳米材料用于活体淋巴结显像

通过水热法,以油酸和两亲性聚乙烯吡咯烷酮(PVP)为协同表面配体,一步水热合成水溶性稀土上转换发光纳米材料(NaYF4:20％ Yb 1％ Tm).稀土纳米粒径尺寸平均为16 nm,在水溶液中稳定单分散,具有较强上转换发光.具有较低的细胞毒性,可用于上转换发光细胞成像.并进一步用于活体淋巴结显像,表现出高的信噪比.     

多重响应性介孔二氧化硅纳米微球的制备及载药研究

采用溶胶凝胶法制备了以油酸稳定的Fe3O4为核, 十六烷基三甲基溴化铵(CTAB)为模板剂的磁响应性的介孔二氧化硅纳米微球; 通过孔道内修饰羧基和巯基, 链转移反应修饰线性的聚(N-异丙基丙烯酰胺-co-N-羟甲基丙烯酰胺)共聚物得到多重响应性的介孔二氧化硅纳米微球P(NIPAM-co-NHMA)@M-MSN(-COOH). 利用Brunauer-Emmett-Teller (BET)、振动样品磁强计(VSM)、透射电子显微镜(TEM)、紫外光谱(UV/Vis)表征了微球的物理化学性质. 阿霉素(DOX)被用作模型药物研究了这种多重响应性的介孔二氧化硅纳米微球作为药物载体的载药及药物释放行为, 结果显示这种纳米微球载药率高达48%, 药物释放呈现对温度和pH的双重响应性, 可以实现对药物的控制释放.     

Fabrication and characterization of mesoporous Co3O4 core/mesoporous silica shell nanocomposites

A mesoporous Co(3)O(4) core/mesoporous silica shell composite with a variable shell thickness of 10-35 nm was fabricated by depositing silica on Co(3)O(4) superlatticed particles. The Brunauer-Emmett-Teller (BET) surface area of the composite with a shell thickness of ca. 2.0 nm was 238.6 m(2)/g, which varied with the shell thickness, and the most frequent pore size of the shell was ca. 2.0 nm. After the shell was eroded with hydrofluoric acid, mesoporous Co(3)O(4) particles with a pore size of ca. 8.7 nm could be obtained, whose BET surface area was 86.4 m(2)/g. It is proposed that in the formation of the composite the electropositive cetyltrimethylammonium bromide (CTAB) micelles were first adsorbed on the electronegative Co(3)O(4) particle surface, which directed the formation of the mesoporous silica on the Co(3)O(4) particle surface. Electrochemical measurements showed that the core/shell composites exhibited a higher discharge capacity compared with that of the bare Co(3)O(4) particles.     

Core-shell Ag@SiO2@mSiO2 mesoporous nanocarriers for metal-enhanced fluorescence

A novel mesoporous nanocarrier consisting of a silver core, a silica spacer with controlled thickness and a fluorophores-loaded mesoporous silica shell was fabricated for the metal-enhanced fluorescence (MEF) and F?rster resonance energy transfer (FRET) effects.