Electrical characterization of an individual nanowire using flexible nanoprobes fabricated by atomic force microscopy-based manipulation

Nanowires have emerged as promising one-dimensional materials with which to construct various nanocircuits and nanosensors.However,measuring the electrical properties of individual nanowires directly remains challenging because of their small size,thereby hindering the comprehensive understanding of nanowire-based device performance.A crucial factor in achieving reliable electrical characterization is establishing well-determined contact conditions between the nanowire sample and the electrodes,which becomes particularly difficult for soft nanowires.Introduced here is a novel technique for measuring the conductivity of an individual nanowire with the aid of automated nanomanipulation using an atomic force microscope.In this method,two nanowire segments cut from the same silver nanowire are positioned onto a pair of gold electrodes,serving as flexible nanoprobes to establish controllable contact with the sample.By changing the contact points along the nanowire sample,conductivity measurements can be performed on different regions,thereby eliminating the influence of contact resistance by analyzing multiple current–voltage curves.Using this approach,the resistivity of a 100-nm-diameter silver nanowire is determined to be 3.49×10^(−8)Ωm.

Specific Recognition of Breast Cancer Cells In Vitro Using Near Infrared-Emitting Long-Persistence Luminescent Zn_3Ga_2Ge_2O_(10):Cr^(3+)Nanoprobes

In this paper, near-infrared emitting long-persistence luminescent Zn3Ga2Ge2O10:Cr3?(ZGG) nanoparticles with diameters of 30–100 nm and bright luminescence were prepared by a sol–gel synthesis method. After the surface amination, the nanoparticles were further bioconjugated with breast cancer-specific monoclonal antibody(anti-Ep CAM) to form ZGG-Ep CAM nanoprobes which can specifically target breast cancer cell lines(MCF7) in vitro. The results of in vitro images show that the luminescence signals from the cells treated with ZGG-Ep CAM nanoprobes are stronger than those from cells treated with ZGG-unconjugated antibody, indicating that the prepared ZGG-Ep CAM nanoprobes possessed excellent specific recognition capability. Furthermore, due to their long afterglow properties, the imaging could persist more than 1 h. Therefore, these nanoprobes could not only provide a high specificity detection method for cancer cells but also realize the long-time monitoring. Developed near-infrared emitting long-persistence luminescent nanoprobes will be expected to find new perspectives for cell therapy research and diagnosis applications.

Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer

How to trigger strong anti-tumor immune responses has become a focus for tumor therapy.Here,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy(PDT)and enhanced immunotherapy.Ce6 photosensitizer was attached on manganese dioxide(MnO2)nanoparticles,and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes.The iPS-MnO2@Ce6 actively targeted in vivo tumors,the acidic microenvironment triggered interaction between MnO2 and H2O2,released large quantities of oxygen,alleviated hypoxia in tumor.Upon PDT,singlet oxygen formed,broken iPSs released tumor-shared antigens,which evoked an intensive innate and adaptive immune response against the tumor,improving dendritic cells matured,effector T cells,and natural killer cells were activated.Meanwhile,regulatory T cells were reduced,and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6(P<0.05).The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor.Human iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.

Controllable Synthesis of Fluorescent Carbon Dots and Their Detection Application as Nanoprobes

Carbon dots(CDs), as a new member of carbon nanomaterial family, have aroused great interest since their discovery in 2004. Because of their outstanding water solubility, high sensitivity and selectivity to target analytes, low toxicity, favorable biocompatibility, and excellent photostability, researchers from diverse disciplines have come together to further develop the fundamental properties of CDs. Many methods for the production of CDs have been reported, therein, hydrothermal and solvothermal technology needs simple equipments, and microwave synthesis needs less reaction time, hence these methods become current common synthesis methods, in which many precursors have been applied to produce CDs. Due to their excellent fluorescence, CDs have made impressive strides in sensitivity and selectivity to a diverse array of salt ions,organic/biological molecules and target gases. The development of CDs as nanoprobes is still in its infancy, but continued progress may lead to their integration into environmental and biological applications. Hydrothermal,solvothermal, and microwave synthesis of fluorescent carbon dots and their detection applications as nanoprobes in salt ions, organic/biological molecules, and target gases will be reviewed.

Imaging-guided precision oncotherapy mediated by nanoprobes: From seeing to curing

Malignant tumors are the main diseases threatening human life. Using precise theranostics to diagnose and cure tumors has emerged as a new method to improve patient survival. Based on the current development of precise tumor imaging, image-guided tumor therapy has received widespread attention because it is beneficial for developing precise treatment of tumors, has the potential to improve the efficacy of tumor therapy and reduce the incidence of adverse side effects. Nanoprobes, which are nanomaterial functionalized with specific biomolecules, have intrigued intense interest due to their great potential in monitoring biorecognition and biodetection evens. Benefiting from the unique advantages of nanomaterials, including the easy surface functionalization, the unique imaging performances, and the high drug loading capacity, nanoprobes have become a powerful tool to simultaneously realize tumor precise imaging, diagnosis, and therapy. This review introduces the non-invasive tumor precise imaging and highlights the recent advances of image-guided oncotherapy mediated by nanoprobes in anti-tumor drug delivery, tumor precise surgical navigation, chemodynamic therapy, and phototherapy. Finally, a perspective on the challenge and future direction of nanoprobes in imaging-guided tumor theranostics is also discussed.

Rare earth fluorescent nanoprobes with minimal side effects enable tumor microenvironment activation for chemotherapy

Chemotherapy,the use of antitumor drugs to kill cancer cells,is currently one of the most effective treatments for cancer.However,serious toxic side effects caused by long-term drug accumulation can cause significant damage to the body,which limits the clinical application of antitumor drugs.In this study,a novel RENPs@DOX-Fe nanoprobe(NP) was constructed by coating the surface of rare earth nanomaterials(NaLuF_(4):Yb,Er) with a complex formed by doxorubicin(DOX) and iron ion(Ⅲ).Due to the low toxicity of anthracycline-metal complexes,the damage to normal cells is reduced.The unique acidic microenvironment in tumor cells facilitates the decomposition and gradual release of DOX from the DOX-Fe complex.In addition,the DOX-Fe complex can convert near-infrared(NIR) light into heat energy,which promotes the decomposition of the complex,further enhancing the release of DOX in the tumor environment.The change of ratio fluorescence of rare earth nanomaterials at 660 and 1550 nm after DOX release enables visual monitoring of drug release,which can potentially improve the chemotherapeutic effect.In vitro experiments established that RENPs@DOX-Fe NPs with NIR illumination had good therapeutic efficacy in tumors.This work provides new insights into designing tumor microenvironment-responsive nanoprobes for chemotherapy with minimal side effects.

Advances in nanoprobes-based immunoassays

Immunoassay is a powerful technique that uses highly specific antigenantibody interactions to detect biochemical targets such as proteins and toxins.As a diagnostic tool,immunoassay is employed in the screening,diagnosis,and prognosis of diseases,which are crucial for the grasp and control of patient conditions in clinical practice.With the rapid development of nanotechnology,immunoassays based on nanoprobes have attracted more and more attention due to the advantages of high sensitivity,specificity,stability,and versatility.These nanoprobes are nanoscale particles that can act as signal carriers or targeting agents for immunoassays.In this paper,we review the recent advances in various types of nanoprobes for immunoassays,such as colloidal gold,quantum dots,magnetic nanoparticles,nanozymes,aggregation-induced emission,and up-conversion nanoparticles.The effect of the nanoprobe construction and synthesis methods on their detection performance deserves to be studied in depth.We also compare their detection ranges and limits in different immunoassay methods,such as lateral flow immunoassays,fluorescent immunoassays,and surface-enhanced Raman scattering immunoassays.Moreover,we discuss the benefits and challenges of nanoprobes in immunoassays and provide insights into their future development.This study aims to offer a comprehensive and critical perspective on the role of nanoprobes in the field of immunoassays.

Inorganic imaging nanoprobes for breast cancer diagnosis

Breast cancer is one of the most prevalent cancers worldwide,and early diagnosis and screening are vital to its successful treatment.Although medical imaging methods can assist in the early detection of breast cancer,imaging methods that are currently used for clinical diagnosis have drawbacks,such as low sensitivity and accuracy.Contrast agents are often used in diagnostic imaging to address these drawbacks.Nanocontrast agents have attracted considerable attention in recent years due to their unique physicochemical characteristics.Among these agents,inorganic nanoprobes have been substantially developed through improvements in synthesis techniques and pairings with other organic molecules.This paper mainly summarizes the specific applications of inorganic nanoprobes in the magnetic resonance imaging,fluorescence imaging,radionuclide imaging,and bimodal/multimodal imaging of breast cancer.

Recent progress in engineering near-infrared persistent luminescence nanoprobes for time-resolved biosensing/bioimaging

Persistent luminescence nanoprobes (PLNPs) can remain luminescent after ceasing excitation.Due to the ultra-long decay time of persistent luminescence (PersL),autofluorescence interference can be efficiently eliminated by collecting PersL signal after autofluorescence decays completely,thus the imaging contrast and sensing sensitivity can be significantly improved.Since near-infrared (NIR) light shows reduced scattering and absorption coefficient in penetrating biological organs or tissues,near-infrared persistent luminescence nanoprobes (NIR PLNPs) possess deep tissue penetration and offer a bright prospect in the areas of in vivo biosensing/bioimaging.In this review,we firstly summarize the design of different types of NIR PLNPs for biosensing/bioimaging,such as transition metal ions-doped NIR PLNPs,lanthanide ions-doped NIR PLNPs,organic molecules-based NIR PLNPs,and semiconducting polymer self-assembled NIR PLNPs.Notably,organic molecules-based NIR PLNPs and semiconductor self-assembled NIR PLNPs,for the first time,were introduced to the review of PLNPs.Secondly,the effects of different types of charge carriers on NIR PersL and luminescence decay of NIR PLNPs are significantly emphasized so as to build up an in-depth understanding of their luminescence mechanism.It includes the regulation of valence band and conduction band of different host materials,alteration of defect types,depth and concentration changes caused by ion doping,effective radiation transitions and energy transfer generated by different luminescence centers.Given the design and potential of NIR PLNPs as long-lived luminescent materials,the current challenges and future perspective in this rapidly growing field are also discussed.

Tracing of dye molecules in living plants through NaGdF_4:Yb^(3+),Er^(3+)fluorescent nanoprobes

In this paper, we demonstrated trace of dye molecules in living plants. The NaGdF4:Yb^(3+),Er^(3+) nanoparticles probe was used to detect the rhodamine B(RhB) in bean sprout. It is found that the fluorescencedye can be efficiently imbibed during the growing process and the absorbance presented a position dependence effect, which was supported by the upconversion spectra and the fluorescent image characterization. In addition, the concentration of the residual RhB in bean sprout can be efficiently traced by the synthesized probe based on the fluorescent resonant energy transfer. Finally, the relation between the excitation power, concentration and the ratio of yellow to green emission are discussed in detail. These results can be helpful in understanding the RhB dye molecules absorbance process in vegetable growth and provide an efficient way to trace the residual dyes in vivo plant.

Design of SERS nanoprobes for Raman imaging:materials, critical factors and architectures

Raman imaging yields high specificity and sensitivity when compared to other imaging modalities, mainly due to its fingerprint signature. However, intrinsic Raman signals are weak, thus limiting medical applications of Raman imaging. By adsorbing Raman molecules onto specific nanostructures such as noble metals, Raman signals can be significantly enhanced, termed surfaceenhanced Raman scattering(SERS). Recent years have witnessed great interest in the development of SERS nanoprobes for Raman imaging. Rationally designed SERS nanoprobes have greatly enhanced Raman signals by several orders of magnitude, thus showing great potential for biomedical applications.In this review we elaborate on recent progress in design strategies with emphasis on material properties,modifying factors, and structural parameters.

Highly efficient luminescent Ⅰ-Ⅲ-Ⅵ semiconductor nanoprobes based on template-synthesized CuInS2 nanocrystals

CuInS2 semiconductor nanocrystals (NCs) exhibit large absorption coefficient, size-dependent photoluminescence and low toxicity, making them excellent candidates in a variety of bioapplications. However, precise control of both their composition and morphology to improve the luminescent efficiency remains a great challenge via conventional direct synthesis. Herein, we present a novel low-temperature template synthesis of highly efficient luminescent CuInS2 nanoprobes from In2S3 NCs via a facile cation exchange strategy. The proposed strategy enables synthesis of a series of CuInS2 NCs with broad size tunability from 2.2 to 29.6 nm. Through rationally manipulating the stoichiometry of Cu/In, highly efficient luminescence of CuInS2 with the maximum quantum yield of 28.6% has been achieved, which is about one order of magnitude improvement relative to that of directly synthesized NCs. By virtue of the intense emission of CuInS2 nanoprobes, we exemplify their application in sensitive homogeneous biodetection for an important biomolecule of adenosine triphosphate (ATP) with the limit of detection down to 49.3 nM. Moreover, the CuInS2 nanoprobes are explored for ATP-targeted cancer cell imaging, thus revealing their great potentials in the field of cancer diagnosis and prognosis.

On-demand degradable magnetic resonance imaging nanoprobes

Theranostic nanoprobes can potentially integrate imaging and therapeutic capabilities into a single platform,offering a new personalized cancer diagnostic tool.However,there is a growing concern that their clinical application is not safe,particularly due to metal-containing elements,such as the gadolinium used in magnetic resonance imaging(MRI).We demonstrate for the first time that the photothermal melting of the DNA duplex helix was a reliable and versatile strategy that enables the on-demand degradation of the gadolinium-containing MRI reporter gene from polydopamine(PDA)-based theranostic nanoprobes.The combination of chemotherapy(doxorubicin)and photothermal therapy,which leads to the enhanced anti-tumor effect.In vivo MRI tracking reveals that renal filtration was able to rapidly clear the free gadolinium-containing MRI reporter from the mice body.This results in a decrease in the long-term toxic effect of theranostic MRI nanoprobes.Our findings may pave the way to address toxicity issues of the theranostic nanoprobes.

Vacancy-defect-dipole amplifies the thermoacoustic conversion efficiency of carbon nanoprobes

The immense potential of carbon nanoprobes(CNPs)for using as contrast agents has propelled much recent research and development in the field of thermoacoustic(TA)molecular imaging,while the proper engineering and design of such materials with required high TA conversion efficiency is still a highly challenging task.In this work,we proposed a controllable strategy to amplify the TA conversion efficiency of the CNPs by constructing vacancy defect(VD)dipoles,and systematically demonstrated the amplification mechanism through theoretical and experimental investigations.First-principles calculation results indicate that,when a carbon atom is removed from the CNPs by chemical approach,owing to local electron density redistribution,the VDs are formed at the positions of the original carbon atoms and act as the structural origin of permanent electric dipoles with the dipole moment several orders higher than that of non-defect sites.Under pulsed microwave irradiation,the VD dipoles are polarized repeatedly and significantly contribute to the conversion efficiency from absorbed electromagnetic waves to ultrasound through enhanced dielectric relaxation losses.We experimentally synthesized graphene samples with different VD densities and VD types to demonstrate the efficiency of the proposed strategy,and results coincide well with the theoretical proposition.This work offers feasible guidance to the systematic development and rational design of new high-conversion-efficiency TA CNPs via VD engineering.

Nanoprobes in biomedical detection

Environmental problems caused by the development of nanotechnology have threatened human health. Investigating the biomedical effects of nanomaterials can help to solve these environmental safety issues. In studies on the biomedical effects of nanomaterials, several types of novel nanoscale probes that allow reliable, sensitive, accurate and rapid biomedical detection have emerged. We summarize recent developments in three categories of these nanoprobes, including noble metal nanocluster probes, carbon-based nanostructured probes, and unnatural amino acid-based probes. Besides reviewing the utility of different nanoprobes in cell imaging and protein detection, we also discuss the molecular mechanism of nanoprobe detection. Perspectives of novel nanoprobe design based on molecular details of biomedical detection are presented.

SERS nanoprobes for bio-application

The ability to tune the size, shape, composition and surface properties impart nanoparticles with the desired functions for bio-application. This article highlights some of the recent examples in the exploration of metal （e.g., gold and silver） nanoparticles, especially those with magnetic properties and bio-conjugated structures, as theranostic nanoprobes. Such nanoprobes exhibit tunable optical, spectroscopic, magnetic, and electrical properties for signal amplifications. Examples discussed in this article will focus on the nanoproble-enhanced colorimetric detection and surface enhanced Raman scattering （SERS） detection of biomarkers or biomolecules such as proteins and DNAs. The understanding of factors controlling the biomolecular interactions is essential for the design of SERS nanoprobes with theranostic functions.

Aptamer-Anchored Rubrene-Loaded Organic Nanoprobes for Cancer Cell Targeting and Imaging

Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus impera-tive.To move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent nanoprobes.The aptamer-modified organic nanop-robes integrated the best features of the organic light-emitting materials and the aptamers,thus endowing them with excellent cell-targeting capabil-ity,high stability,and good biocompatibility.By using this general method,a variety of biocompatible and highly bright organic fluorescent nanoprobes based on novel organic light-emitting materials with specific recognition could be easily constructed for real-time biosensing and long-term biomedical imaging.

The hard X-ray nanoprobe beamline at the SSRF

The hard X-ray nanoprobe beamline BL13U is a phase-Ⅱ beamline project at the Shanghai Synchrotron Radiation Facility.The beamline aims to enable comprehensive experiments at high spatial resolutions ranging from 50 to 10 nm. The X-ray energy range of the beamline, 5–25 keV, can detect most elements in the periodic table. Two operating modes were designed to accommodate the experimental requirements of high-energy resolution or high photon flux, respectively. X-ray nanofluorescence, nanodiffraction, and coherent diffraction imaging are developed as the main experimental techniques for BL13U. This paper describes the beamline optics, end station configurations, experimental methods under development, and preliminary test results. This comprehensive overview aims to provide a clear understanding of the beamline capabilities and potential applications.

Organic Nanoprobes for Fluorescence and ^19F Magnetic Resonance DuaI-Modality Imaging

Multimodal imaging techniques have been demonstrated to be greatly advantageous in achieving accurate diagnosis and gained increasing attention in recent decades. Herein, we present a new strategy to integrate the complementary modalities of I9F magnetic resonance imaging （19F MRI） and fluorescence imaging （FI） into a polymer nanoprobe composed of hydrophobic fluorescent organic core and hydrophilic fluorinated polymer shell. The alkyne-terminated fluorinated copolymer （Pn） of 2,2,2-trifluoroethyl acrylate （TFEA） and poly（ethylene glycol） methyl ether acrylate （PEGA） was first prepared vie atom transfer radical polymerization （ATRP）. The PEGA plays an important role in both improving ^19F signal and modulating the hydrophilicity of Pn. The alkynyl tail in Pn is readily conjugated with azide modified tetra-phenylethylene （TPE） through click chemistry to form azo polymer （TPE-azo-Pn）. The core-shell nanoprobes （TPE-P3N） with an average particle size of 57.2±8.8 nm are obtained via self-assembly with ultrasonication in aqueous solution. These nanoprobes demonstrate high water stability, good biocompatibility, strong fluorescence and good ^19F MRI performance, which present great potentials for simultaneous fluorescence imaging and ^19F-MR imaging.

Lanthanide-doped near-infrared Ⅱ luminescent nanoprobes for bioapplications

Luminescent biosensing in the second nearinfrared(NIR-II) region is featured with superior spatial resolution and high penetration depth by virtue of the suppressed scattering of long-wavelength photons. Hitherto, the reported NIR-II nanoprobes are mostly based on carbon nanotubes, organic fluorophores or semiconducting quantum dots. As an alternative, trivalent lanthanide ions(Ln3+) doped nanoparticles have been emerging as a novel class of promising nanoprobes. In this review, we highlight the recent progress in the design of highly efficient Ln3+-doped NIR-II nanoparticles towards their emerging bioapplications, with an emphasis on autofluorescence-free bioimaging, sensitive bioassay, and accurate temperature sensing. Moreover, some efforts and challenges towards this rapidly expanding field are envisioned.