Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Apoptotic bodies encapsulating Ti2N nanosheets for synergistic chemo-photothermal therapy.

Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV family, offer distinct advantages in terms of size, availability and membrane properties, but have been neglected for a long time. Here, using ABs and Ti2N nanosheets, we propose a novel drug delivery system (Ti2N-DOX@ABs), which exhibit a homologous targeting ability for dual-strategy tumor therapy with intrinsic biological property. The experimental results demonstrate that such a drug delivery system possesses a drug loading capacity of 496.5% and a near-infrared photothermal conversion efficiency of 38.4%. In addition, the investigation of drug internalization process proved that Ti2N-DOX@ABs featured a supreme biocompatibility. Finally, the dual-strategy response based on photothermal and chemotherapeutic effects was studied under near-infrared laser radiation. This work explores the opportunity of apoptosome membranes in nanomedicine systems, which provides a technical reference for cancer-oriented precision medicine research.

Understanding the Electrochemical Extraction of Lithium from Ultradilute Solutions.

The electrochemical extraction of lithium (Li) from aqueous sources using electrochemical means is a promising direct Li extraction technology. However, to this date, most electrochemical Li extraction studies are confined to Li-rich brine, neglecting the practical and existing Li-lean resources, with their overall extraction behaviors currently not fully understood. More still, the effect of elevated sodium (Na) concentrations typically found in most Li-lean water sources on Li extraction is unclear. Hence, in this work, we first understand the electrochemical Li extraction behaviors from ultradilute solutions using spinel lithium manganese oxide as the model electrode. We discovered that Li extraction depends highly on the Li concentration and cell operation current density. Then, we switched our focus on low Li to Na ratio solutions, revealing that Na can dominate the electrostatic screening layer, reducing Li ion concentration. Based on these understandings, we rationally employed pulsed electrochemical operation to restructure the electrode surface and distribute the surface-adsorbed species, which efficiently achieves a high Li selectivity even in extremely low initial Li/Na concentrations of up to 1:20,000.

A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

Highly sensitive and specific detection of silver ions using a dual-color fluorescence co-localization strategy.

Ag+ ions are widely used in various fields of human life due to their unique properties and they threaten the environment and human health. The traditional methods for Ag+ detection commonly suffer from disadvantages including limited sensitivity, expensive equipment and complicated operating steps. Herein, we developed a highly specific dual-color fluorescence co-localization (DFC) strategy based on the C-Ag+-C structure for Ag+ detection. In this strategy, Ag+ ions can be captured to form C-Ag+-C base pairs, and these ions enable single-stranded DNAs to form double strands. The DFC strategy can exclude nonspecific interaction sites and greatly improve the sensitivity and specificity. By DFC of the QDs and Cy5 linked to the DNA strands, highly sensitive Ag+ detection was achieved in the concentration range from 0.14 pM to 200 nM, with a limit of detection (LOD) of 0.14 pM. Moreover, this method has been applied for the detection of Ag+ ions in real environmental samples with satisfactory recoveries. We believe that the DFC strategy is promising for Ag+ detection.

Fluorescence Super-Resolution Imaging Chip for Gene Silencing Exosomes.

Tumor cell-derived extracellular vesicles and their cargo of bioactive substances have gradually been recognized as novel biomarkers for cancer diagnosis. Meanwhile, the PD-L1 (Programmed Death-Ligand 1) protein, as an immune checkpoint molecule, is highly expressed on certain tumor cells and holds significant potential in immune therapy. In comparison to PD-L1 monoclonal antibodies, the inhibitory effect of PD-L1 siRNA (small interfering RNA) is more advantageous. In this article, we introduced a microfluidic chip integrating cell cultivation and exosome detection modules, which were intended for the investigation of the gene silencing effect of PD-L1 siRNA. Basically, cells were first cultured with PD-L1 siRNA in the chip. Then, the secreted exosomes were detected via super-resolution imaging, to validate the inhibitory effect of siRNA on PD-L1 expression. To be specific, a "sandwich" immunological structure was employed to detect exosomes secreted from HeLa cells. Immunofluorescence staining and DNA-PAINT (DNA Point Accumulation for Imaging in Nanoscale Topography) techniques were utilized to quantitatively analyze the PD-L1 proteins on HeLa exosomes, which enabled precise structural and content analysis of the exosomes. Compared with other existing PD-L1 detection methods, the advantages of our work include, first, the integration of microfluidic chips greatly simplifying the cell culture, gene silencing, and PD-L1 detection procedures. Second, the utilization of DNA-PAINT can provide an ultra-high spatial resolution, which is beneficial for exosomes due to their small sizes. Third, qPAINT could allow quantitative detection of PD-L1 with better precision. Hence, the combination of the microfluidic chip with DNA-PAINT could provide a more powerful integrated platform for the study of PD-L1-related tumor immunotherapy.

Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and Stability.

Surface-enhanced Raman spectroscopy (SERS) is a promising technology for wearable sensors due to its fingerprint spectrum and high detection sensitivity. However, since SERS-activity is sensitive to both the distribution of "hotspots" and excitation angle, it is profoundly challenging to develop a wearable SERS sensor with high stability under various deformations during movements. Herein, inspired by omnidirectional light-harvesting of the compound eye of Xenos Peckii, a wearable SERS sensor is developed using omnidirectional plasmonic nanovoids array (OPNA), which is prepared by assembling a monolayer of metal nanoparticles into the artificial plasmonic compound-eye (APC). Specifically, APC is an interconnected frame containing omnidirectional "pockets" and acts as an "armour", not only rendering a broadband and omnidirectional enhancement of "hotspots" in the delicate nanoparticles array, but also maintaining an integrity of the "hotspots" against external mechanical deformations. Furthermore, an asymmetry super-hydrophilic pattern is fabricated on the surface of OPNA, endowing the hydrophobic OPNA with the ability to spontaneously extract and concentrate the analytes from sweat. Such an armored SERS sensor can enable the wearable and in situ analysis with high sensitivity and stability, exhibiting great potential in point-of-care analysis.

Triple-color fluorescence co-localization of PD-L1-overexpressing cancer exosomes.

Programed cell death ligand 1 (PD-L1) is a protein biomarker overexpressed on exosomes derived from tumor cells. It plays an important role in tumor diagnosis, screening, evaluation of therapeutic efficacy, and prognosis. In this study, a facile method is presented to detect PD-L1-overexpressing cancer exosomes with high specificity and sensitivity. First, gold nanospheres (GNSs) were attached to the bottom of an eight-well chambered slide by electrostatic adsorption, forming the detection substrate. Then, Cy5-labeled CD63 aptamers (i.e., the capture probes) were modified on the GNSs by Au-S bond. After adding samples containing target exosomes which were stained by membrane dyes DiI in advance, FAM-labeled PD-L1 aptamers (i.e., the immunoprobes) were added to recognize PD-L1 on the target exosomes. By triple-color fluorescence co-localization (TFC) of the Cy5, DiI, and FAM channels, highly sensitive and reliable detection of the PD-L1-overexpressing exosomes was achieved in the concentration range 7.78 × 101 to 7.78 × 104 particles/mL with a detection limit down to 6 particles/mL. The advantages of the proposed detection method include the following; first, the detection substrate is easy to prepare and convenient to clean. Second, the TFC strategy can completely exclude nonspecific reaction sites and thus significantly improves the accuracy. Such a facile and reliable detection method holds a great potential in exosome-based cancer theranostics. In this paper, we proposed a triple-color fluorescence co-localization (TFC) strategy to significantly improve the reliability of exosome detection and the detection substrate is easy to prepare and convenient to clean. In addition, the LOD is down to 6 particles/mL, which is quite low compared with other detection methods.

Telomerase detection using a DNA-PAINT strategy.

Telomerase plays an important role in maintaining the length of telomere during cell division and is recognized as a new kind of biomarkers for cancer diagnosis. In this work, we present a brand new telomerase detection strategy based on a DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) like strategy. With an extraordinary spatial resolution (∼10 nm), the DNA-PAINT based strategy offers several advantages. First, it avoids complicated polymerase chain reaction and electrophoresis procedures. Second, it enables super resolution imaging of the reaction products with a high signal-to-noise ratio and facilitates the location of telomeric elongation sites on the single particle level, which results in a high sensitivity. Third, the detection scheme of the DNA-PAINT strategy allows directin situvisualization of the telomeric elongation process, which has never been achieved before. All these advantages make the DNA-PAINT telomerase detection strategy significant for dynamic investigation of telomerase related physiological processes as well as cancer diagnosis.

Interference-free SERS nanoprobes for labeling and imaging of MT1-MMP in breast cancer cells.

The expression of membrane type-1 matrix metalloproteinase (MT1-MMP) in cancer cells is critical for understanding the development, invasion and metastasis of cancers. In this study, we devised an interference-free surface-enhanced Raman scattering (SERS) nanoprobe with high selectivity and specificity for MT1-MMP. The nanoprobe was comprised of silver core-silica shell nanoparticle with a Raman reporter tag (4-mercaptobenzonitrile) embedded in the interface. Moreover, the nitrile group in 4-mercaptobenzonitrile shows a unique characteristic peak in the Raman-silent region (1800-2800 cm-1), which eliminates spectral overlapping or background interference in the Raman fingerprint region (500-1800 cm-1). After surface modification with a targeting peptide, the nanoprobe allowed visualization and evaluation of MT1-MMP in breast cancer cells via SERS spectrometry. This interference-free, peptide-functionalized SERS nanoprobe is supposed to be conducive to early diagnosis and invasive assessment of cancer in clinical settings.

Simultaneous detection of multiple exosomal microRNAs for exosome screening based on rolling circle amplification.

Exosomal microRNAs (miRNAs) have attracted great attention as predictive and prognostic biomarkers of cancer. Profiling of miRNAs plays a key role in the effective diagnosis of cancers. However, simultaneous quantification of multiple miRNAs is challenging due to their homology and low abundance especially in exosomes. Here, we developed a sensitive detection method for multiple exosomal miRNAs with the help of rolling circle amplification (RCA). In contrast of the traditional ways, this method takes the advantages of both the multiplex sensing ability and the simplicity of RCA. Specifically, multiple exosomal miRNAs from different cell lines were replicated simultaneously through RCA and detected using designed molecular beacons (MBs). miRNA-21, miRNA-122 and miRNA-155 were chosen as the targets, which are overexpressed in cancers. Normalized fluorescence intensities of MB were used to imply the relative concentrations of these miRNAs. The obtained relative miRNAs expression levels could be used to distinguish the breast cancer exosome from normal one. If the varieties of the detected exosomal miRNAs are abundant enough, the concentration ratios of miRNAs could basically indicate the corresponding exosome and exosome screening could be realized. Such exosomal miRNA profiling and exosome screening can assist cancer diagnosis, which is promising in clinical application.

Quaternary-Ammonium-Modulated Surface-Enhanced Raman Spectroscopy Effect: Discovery, Mechanism, and Application for Highly Sensitive In Vitro Sensing of Acetylcholine.

Quaternary ammonium (QA) plays multiple roles in biological functions, whose dysregulation may result in multiple diseases. However, how to efficiently detect QA-based materials such as acetylcholine (ACh) still remains a great challenge, especially in complex biological environments. Here, a new effect [called quaternary-ammonium-modulated surface-enhanced Raman spectroscopy (QAM-SERS) effect] is discovered, showing that the existence of QA will modulate the intensity of SERS signals in a concentration-dependent manner. When the QAM-SERS effect is used, a new method is easily developed for in vitro detection of ACh with an extremely high sensitivity and an ultrawide dynamic range. Particularly, the linear dynamic range can be freely tuned to adapt for various physiological samples. As a proof-of-concept experiment, the time-dependent secretion of ACh from PC12 cells was successfully monitored using the QAM-SERS method, which were under either the stimulation of potassium ions or the incubation of drugs. The discovery of the QAM-SERS effect provides an easy and universal strategy for detecting ACh as well as other QA-contained molecules, which can also inspire new insights into the roles that QA could play in biology and chemistry.

A SERS-colorimetric dual-mode aptasensor for the detection of cancer biomarker MUC1.

Human mucin-1 (MUC1) has attracted considerable attention owing to its overexpression in diverse malignancies. Here, for the rapid and efficient detection of MUC1, we present a SERS-colorimetric dual-mode aptasensor, by integrating SERS probes with magnetic separation, which has several distinctive advantages. Using such a dual-mode aptasensor, the colorimetric functionality is distinguishable by the naked eye, providing a fast and straightforward screening ability for the detection of MUC1. Moreover, SERS-based detection greatly improves the detection sensitivity, reaching a limit of detection of 0.1 U/mL. In addition, the combination of SERS and colorimetric method holds the advantages of these two techniques and thereby increases the reliability and efficiency of MUC1 detection. On the one hand, the magnetic nanobeads functionalized with MUC1-specific aptamer were utilized as an efficient capturing substrate for separating MUC1 from biological complex medium. On the other hand, the gold-silver core-shell nanoparticles modified with Raman reporters and the complementary sequences of MUC1 were used as the signal indicator, which could simultaneously report the SERS signal and colorimetric change. This strategy can achieve a good detection range and realize MUC1 analysis in real patients' samples. Thus, we anticipate that this kind of aptasensor would provide promising potential applications in the diagnosis and prognosis of cancers. Graphical abstract.

Profiling of Exosomal Biomarkers for Accurate Cancer Identification: Combining DNA-PAINT with Machine- Learning-Based Classification.

Exosomes are endosome-derived vesicles enriched in body fluids such as urine, blood, and saliva. So far, they have been recognized as potential biomarkers for cancer diagnostics. However, the present single-variate analysis of exosomes has greatly limited the accuracy and specificity of diagnoses. Besides, most diagnostic approaches focus on bulk analysis using lots of exosomes and tend to be less accurate because they are vulnerable to impure extraction and concentration differences of exosomes. To address these challenges, a quantitative analysis platform is developed to implement a sequential quantification analysis of multiple exosomal surface biomarkers at the single-exosome level, which utilizes DNA-PAINT and a machine learning algorithm to automatically analyze the results. As a proof of concept, the profiling of four exosomal surface biomarkers (HER2, GPC-1, EpCAM, EGFR) is developed to identify exosomes from cancer-derived blood samples. Then, this technique is further applied to detect pancreatic cancer and breast cancer from unknown samples with 100% accuracy.

SERS-Activated Platforms for Immunoassay: Probes, Encoding Methods, and Applications.

Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved to date, SERS immunoassays still suffer from some annoying shortcomings. Thus, proposals on how to improve the SERS immunoassay performance are also discussed, as well as future challenges and perspectives, aiming to give brief and valid guidelines for choosing suitable platforms according to particular applications.

Super blinking and biocompatible nanoprobes based on dye doped BSA nanoparticles for super resolution imaging.

As one of the super-resolved optical imaging techniques, single molecule localization microscopy (SMLM) received considerable attention due to its impressive spatial resolution. Compared with other fluorescence imaging techniques, SMLM has one particular request for the fluorophores, that is, continuous 'on' and 'off' behaviors of their signals (referred to as 'blinking'). Hence, we present here a kind of super blinking and biocompatible nanoprobes (denoted as SBNs) for SMLM. The SBNs have two main advantages, first, they possess an outstanding fluorescence blinking. Second, they are biocompatible since they are based on bovine serum albumin (BSA). The SBNs are fabricated by doping organic dyes into BSA nanoparticles. We fabricated two kinds of SBNs, one was doped with Alexa Fluor 647 (A647) and the other was doped with Alexa Fluor 594 (A594). Especially for A594 doped SBNs, the improved blinking of A594 doped SBNs induced a better localization precision as compared with A594 alone. Moreover, SMLM imaging of breast cancer cells and exosomes using the SBNs was successfully realized with high spatial resolutions. The work demonstrated here provides a new strategy to prepare novel kinds of super blinking fluorescent agents for SMLM, which broadens the selection of suitable fluorophores for SMLM.

A SERS fiber probe fabricated by layer-by-layer assembly of silver sphere nanoparticles and nanorods with a greatly enhanced sensitivity for remote sensing.

Remote sensing remains a challenge due to its demand for high sensitivity, convenient sampling and rapid response time. Surface enhanced Raman scattering (SERS) spectroscopy is a powerful analytical method for the detection of various samples. Here, aiming at increasing the sensitivity, a novel strategy for the preparation of a SERS probe is demonstrated by using hollow optical fiber tips decorated by layer-by-layer assembly of two kinds of nanoparticles. Specifically, Au@Ag core-shell nanorods and Ag nanospheres with opposite surface charge were assembled layer-by-layer on the tip of hollow optical fibers through electrostatic interaction. Then, much more hotspots are generated due to the close gap between the nanorods and nanospheres in the resultant 3D structure, which can lead to a dramatically enhanced SERS activity of the probe compared with that fabricated by pure silver sphere nanoparticles or nanorods. On the other hand, taking the advantages of the vibration spectroscopic fingerprints property of SERS spectra and the long-distance communication capacity of optical fibers, the remote online detection of biological species including proteins, funguses and cells can be easily achieved within a few minutes. Therefore, such a novel kind of optical fiber-SERS sensor holds great potential for the rapid detection of a wide range of samples due to its superiority of simplicity and high sensitivity.

Atomic Force Microscope Guided SERS Spectra Observation for Au@Ag-4MBA@PVP Plasmonic Nanoparticles.

Recently polymer encapsulated surface-enhanced-Raman-scattering (SERS) probes with internal noble metal core-shell structure has found growing applications in biomedical applications. Here we studied the SERS spectra of Au@Ag-4MBA@PVP (4MBA: 4-mercaptobenzoic acid; PVP: polyvinylpyrrolidone) plasmonic nanoparticles produced from a chemical reduction method. By linking the atomic force microscope (AFM) with the homebuilt confocal Raman spectrometer thus to use AFM images as guidance, we realized the measurement of the SERS spectra from separated nanoparticles. We investigated the cases for single nanoparticles and for dimer structures and report several observed results including SERS spectra linearly scaled with laser power, abrupt boosting and abnormal shape changing of SERS spectra for dimer structures. Based on the finite element method simulation, we explained the observed ratio of SERS signals between the dimer structure and the single nanoparticle, and attributed the observed abnormal spectra to the photothermal effect of these plasmonic nanoparticles. Our study provides valuable guidance for choosing appropriate laser power when applying similar SERS probes to image biological cells.

Combining Multiplex SERS Nanovectors and Multivariate Analysis for In Situ Profiling of Circulating Tumor Cell Phenotype Using a Microfluidic Chip.

Isolating and in situ profiling the heterogeneous molecular phenotype of circulating tumor cells are of great significance for clinical cancer diagnosis and personalized therapy. Herein, an on-chip strategy is proposed that combines size-based microfluidic cell isolation with multiple spectrally orthogonal surface-enhanced Raman spectroscopy (SERS) analysis for in situ profiling of cell membrane proteins and identification of cancer subpopulations. With the developed microfluidic chip, tumor cells are sieved from blood on the basis of size discrepancy. To enable multiplex phenotypic analysis, three kinds of spectrally orthogonal SERS aptamer nanovectors are designed, providing individual cells with composite spectral signatures in accordance with surface protein expression. Next, to statistically demultiplex the complex SERS signature and profile the cellular proteomic phenotype, a revised classic least square algorithm is employed to obtain the 3D phenotypic information at single-cell resolution. Combined with categorization algorithm partial least square discriminate analysis, cells from different human breast cancer subtypes can be reliably classified with high sensitivity and selectivity. The results demonstrate that this platform can identify cancer subtypes with the spectral information correlated to the clinically relevant surface receptors, which holds great potential for clinical cancer diagnosis and precision medicine.

Gold-carbon dots for the intracellular imaging of cancer-derived exosomes.

As a novel fluorescent nanomaterial, gold-carbon quantum dots (GCDs) possess high biocompatibility and can be easily synthesized by a microwave-assisted method. Owing to their small sizes and unique optical properties, GCDs can be applied to imaging of biological targets, such as cells, exosomes and other organelles. In this study, GCDs were used for fluorescence imaging of exosomes. Tumor-specific antibodies are attached to the GCDs, forming exosome specific nanoprobes. The nanoprobes can label exosomes via immuno-reactions and thus facilitate fluorescent imaging of exosomes. When incubated with live cells, exosomes labeled with the nanoprobes can be taken up by the cells. The intracellular experiments confirmed that the majority of exosomes were endocytosed by cells and transported to lysosomes. The manner by which exosomes were taken up and the intracellular distribution of exosomes are unaffected by the GCDs. The experimental results successfully demonstrated that the presented nanoprobe can be used to study the intrinsic intracellular behavior of tumor derived exosomes. We believe that the GCDs based nanoprobe holds a great promise in the study of exosome related cellular events, such as cancer metastasis.