Multifunctional Nanoprobes Research Articles

Tuned Manganese-Impregnated Mesoporous Silica Nanoparticles as a pH-Responsive Dual Imaging Probe.

The limitations of individual imaging modalities have led to significant interest in hybrid imaging methods that combine the advantages of multiple techniques. The development of diverse dual imaging agents, which offer the exceptional sensitivity of single-photon emission computed tomography (SPECT) and the high spatial resolution of magnetic resonance imaging (MRI), has been addressing the demand for more advanced diagnostic pharmaceuticals. In this study, 99mTc-labeled manganese oxide-loaded mesoporous silica nanoparticles (MSNs), conjugated with folic acid as the targeting moiety and the chelating agent H2pentapa-en-NH2 (99mTc-MnOx-MSN-FA-pa), were developed for targeted SPECT-MRI dual imaging. The toxicity of the nanoparticles was confirmed through an MTT assay, showing >90% viability in HEK-293 and MDA-MB-231 cells at concentrations up to 200 μg/mL, indicating nonsignificant toxicity. Cellular uptake studies showed that folic acid functionalization effectively accentuated tumor-specific intracellular uptake of nanoparticles in MDA-MB-231 cells through folate receptor-mediated endocytosis. Additionally, the radiolabeling yield of 99mTc-MnOx-MSN-FA-pa was found to be 99.6 ± 0.8% (n = 3), and the pH-responsive release of paramagnetic manganese ions increased the r1 relaxivity of the nanoprobe to 11.37 mM-1 s-1. In vivo SPECT imaging demonstrated rapid tracer accumulation in MDA-MB-231 xenografts, with a tumor-to-muscle ratio of 6.01 ± 0.51 at 2 h, and minimal uptake in nontargeted organs. In vivo MRI studies indicated the strongest tumor contrast at 2 h postinjection. Given its desirable contrast enhancement in T1 MRI and SPECT imaging, along with low toxicity, MnOx-MSN-FA-pa shows potential as an effective multifunctional nanoprobe for precise tumor imaging.

Aptamer-Based Electrochemical Biosensing Platform for Analysis of Cardiac Biomarkers.

Monitoring biomarkers secreted by cardiomyocytes is critical to evaluate anticancer drug-induced myocardial injury (MI). Cardiac troponin I (cTnI) is considered the gold standard biomarker for MI. Herein, an electrochemical aptasensor is engineered for cTnI detection based on lanthanide europium metal-organic frameworks (Eu-MOFs) and a hybridization chain reaction-directed DNAzyme strategy. Three types of Eu-MOF morphologies were easily synthesized by changing the solvent, and the Eu-MOF modulated by mixing the solvent of dimethylformamide and H2O (D-Eu-MOF) exhibited the best performance compared to other morphologies of the Eu-MOFs. Multifunctional nanoprobes were constructed from D-Eu-MOF@Pt loaded with natural horseradish peroxidase and combined with an aptamer-initiated nuclear acid hybridization chain reaction to form G-quadruplex/hemin DNAzymes for signal amplification. A novel capture probe is constructed on the basis of DNA nanotetrahedrons modified on screen-printed gold electrodes to enhance the capture of the target and multifunctional nanoprobes for signal amplification. It exhibits a detection limit of 0.17 pg mL-1 and a linear range from 0.5 pg mL-1 to 15 ng mL-1. The practicality of the platform is evaluated by measuring cTnI in real samples and secreted by cardiomyocytes after drug treatment, which provides great potential in drug-induced MI evaluation for clinical application.

Nanoprobe Based on Novel NIR-II Quinolinium Cyanine for Multimodal Imaging.

NIR-II imaging has the advantages of high sensitivity, spatiotemporal resolution, and high penetration depth, thereby serving as a potential alternative to conventional imaging methods. Herein, a novel NIR-II dye IR-1010 (λex/λem = 1010/1058nm) is reported with high quantum yield (3.08%) and good stability, by incorporating p-methoxyphenyl groups into a quinolinium cyanine dye. Then a multifunctional nanoprobe, termed IUFP NPs, is developed by the incorporation of upconversion (UC) nanoparticles (NPs), perfluoro-15-crown-5-ether (PFCE), and IR-1010, to display the novel performance of multimodal imaging. Under the single-wavelength excitation (980nm), IUFP NPs simultaneously emit the NIR-II fluorescence of IR-1010 and visible UC luminescence of UCNPs, and thus realize the UC imaging for cells, and NIR-II fluorescence/photoacoustic/19F magnetic resonance imaging for blood vessels, lymph nodes and tumor in mice. This work affords a novel approach to NIR-II dyes and a general strategy for the design of multimodal imaging probes.

Biocompatible bright orange emissive carbon dots: Multifunctional nanoprobes for highly specific sensing toxic Cr(VI) ions and mitochondrial targeting cancer cell imaging

Although several luminescent-based nanostructured materials are used as cellular imaging probes, creating a biocompatible subcellular imaging probe can be challenging. Instantaneously, it is crucial and urgently needed for certain fluorescent nanoprobes to identify possibly harmful heavy metal ions. We present a straightforward one-pot preparation of bright orange emissive (quantum yield approximately 16 %) Nitrogen/Sulfur co-doped carbon dots (N/S CDs) from citric acid and methylene blue as raw materials that will serve as a specific Cr(VI) ions sensor and an effective mitochondrial labeling in cancer cells. They had several benefits including low ecological impact, facile synthesis, good water solubility, photostability, and high stability. We found that N/S CDs photoluminescence (PL) could be reduced when Cr(VI) ions were present near them, and the PL reduction occurred highly sensitively to the presence of Cr(VI) compared to other metal ions including Cr(III) ions. This specific reduction of PL was due to the non-fluorescent complex formation through the inner filter effect (IFE). The established fluorescence-based sensing technique could serve for Cr(VI) ion quantification with exceptional sensing efficiency in the wide linear range of 7 to 70 μM (R2 = 0.9873), with the limit of detection of 53.5 nM. It was also revealed that the current fluorescent probe could be encouragingly utilized to quantify the concentration of Cr(VI) ions in various water specimens such as tap water. In addition, they were shown to function as a mitochondria-targeting nanoprobe in human cancer cells (ME 180 cells and Hela cells) for cell imaging. Concludingly, it was envisioned that these fluorescent nanoprobes could find a use in real-time monitoring of Cr(VI) ions in water-based ecosystems with ultrahigh sensitivity and cell image tracking via mitochondria labeling as biocompatible nanoprobes.

Multifunctional Nanoprobe Au@Gd-SiO2-HA-Lyp-1/DOX with Dual-Targeting Functions Derived from HA and LyP-1: Diagnostic and Therapeutic Potential for Tumor Lymphatic Metastasis.

To address lymphatic metastasis in lung cancer, we developed the Au@Gd-SiO2-HA-LyP-1 nanoprobe, assessing its diagnostic and therapeutic capabilities. This nanoprobe integrates a Au core with a Gd-SiO2 shell and dual-targeting HA-LyP-1 molecules. We evaluated its size, shape, and functional properties using various characterization techniques, alongside in vivo and in vitro toxicity tests. The spherical nanoprobes have a 50 nm diameter and contain 1.37% Gd. They specifically target lymphatic metastasis sites and tumor cells, showing enhanced MRI contrast and effective, targeted DOX delivery with reduced normal tissue toxicity. The Au@Gd-SiO2-HA-LyP-1 nanoprobe is a promising tool for diagnosing and treating lung cancer lymphatic metastasis, featuring dual-targeting and superior imaging capabilities.

Construction of multifunctional core-shell structure nanoprobe integrating NIR dual-mode optical thermometer and nuclear magnetic imaging

Precise temperature regulation and imaging are critical for in vivo photothermal treatment. The goal of this work is to realize non-contact temperature measurement and imaging in biological tissues by building a multifunctional nano-platform using optical temperature probes and imaging for biological diagnosis and therapy. Here, NIR dual-mode temperature probes of NaYF4: Nd/Yb/Gd@NaNdF4 were designed according to the LIR-I of 4F3/2 → 4I9/2/2F5/2 → 2F7/2 levels in 850 – 1025 nm and LIR-II of 2F5/2 → 2F7/2/4F3/2 → 4I11/2 in 950 – 1100 nm from the emissions of Nd3+/Yb3+. Transmission electron microscope (TEM) and X-ray diffraction (XRD) data of the sample demonstrate its superior dispersibility and accurate structure. The integrated intensity ratio centered around various luminescence intensity peaks is used as a temperature sensor since luminescence intensity is temperature-dependent. Additionally, the temperature sensing capabilities of two ratio temperature sensors were examined under 808 nm laser excitation, utilizing LIR (luminescence intensity ratio) technology. Furthermore, the MRI test indicated that the sample exhibited good imaging capacity when Gd3+ was added. These results assure the auspicious application prospects of the samples in temperature sensing, photothermal therapy, and biomedical imaging.

Multifunctional Eu-doped carbon dots nanoprobe for highly sensitive and selective determination of glutathione in biological fluid and cell imaging

Glutathione (GSH) holds a vital role in biological systems, serving diverse cellular functions. Selective determination of GSH over cysteine (Cys) and homocysteine (Hcy) stays challenging due to the shared functional groups among these biothiols. In this study, a versatile Eu-doped carbon dots (Eu-CDs) nanoprobe has been developed for the exceptionally sensitive and selective detection of GSH in biological fluids. The synthesized Eu-CDs exhibited high solubility in water, stability to salt and pH variations, and consistent fluorescence emission, boasting a quantum yield of 40.67 %. Following the optimization of detection parameters, a robust linear relationship for GSH was established in the concentration range of 0.0–50 μM, with a detection limit of 0.03 μM. The viability of the technique in actual samples was evaluated by successfully measuring the GSH in urine and human serum samples with a range recovery from 90.6 % to 98.5 %. Furthermore, Eu-CDs proved to be exceptionally suitable for imaging Hela cells owing to their low cytotoxicity and remarkable biocompatibility. As a result, the developed fluorescent biosensor demonstrated significant potential for widespread application in clinical diagnostic analyses.

ESIPT-associated fluorescent property and AIE characteristic of multifunctional nanoprobe DPNAP

The DPNAP is a multifunctional nanoprobe designed for selective illumination of fungi and targeted antimicrobial applications. By introducing hydroxyl groups into the DPNAP, the aggregation-induced emission (AIE) characteristic can be obtained. However, its optical properties and underlying theoretical mechanisms are not fully understood. In this work, we explored the stable DPNAP configurations by constructing the potential energy surfaces and elucidated the mechanism of the proton transfer reaction. Our findings indicate that proton transfer occurs through a stepwise reaction with energy barriers of < 10 kcal/mol, owing to the variation in hydrogen-bonding strength as revealed by hydrogen-bond parameters and infrared vibrational analyses. The theoretical fluorescence peak (λcal = 541 nm) based on the optimized structures is consistent with the experimental peak (λexp = 500 nm). The experimental single-fluorescence band is attributed to the overlap of emission spectra of normal structure and single- and double-proton transfer isomers. Moreover, the hydroxyl-induced AIE mechanism is attributed to increased molecular planarity and restricted intramolecular charge transfer in the aggregate state. Understanding of the AIE characteristic and ESIPT mechanism is of fundamental importance in molecular electronics and photonics, and is also beneficial to the development of novel biomedical materials.

Rare Earth Nanoprobes for Targeted Delineation of Triple Negative Breast Cancer and Enhancement of Radioimmunotherapy.

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer invivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both invitro and invivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

The Value of Near-Infrared Multifunctional Nanoprobe Combined with Artificial Intelligence Microsensor Technology in Molecular Diagnosis for Gastric Cancer

Since the symptoms of early gastric cancer patients are not obvious, the majority of new gastric cancer cases are progressive gastric cancer every year. In this paper, we applied nanomedicine technology to design and prepare multifunctional nanoparticles for the diagnosis and treatment of gastric cancer. Through targeted imaging of gastric cancer, combined with phototherapy and the prepared nanoprobes are applied to the ectopic transplantation tumor model of gastric cancer. Meanwhile, a fluorescent microsensor based on graphene oxide and deoxyribonuclease is constructed in order to realize the rapid detection of gastric cancer exosomes. The near-infrared multifunctional nanoprobe is combined with artificial intelligence microsensor technology and applied to the molecular diagnosis of gastric cancer. The results shows that the P-P-I-M+ laser irradiation group has the highest fluorescence intensity and its average fluorescence intensity is 2.04 times higher than that of the P-P-I+ laser irradiation group. The relative cell viability of P-P-M+ laser irradiation group, P-P-I+ laser irradiation group and P-P-I-M+ laser irradiation group are 62.5%, 41.9% and 19.3%, respectively. Therefore, the method in this paper can reduce the non-specific toxicity to other organs as well as exert the effect of combining the diagnosis and treatment of gastric cancer.

Intracellular MicroRNA Imaging and Specific Discrimination of Prostate Cancer Circulating Tumor Cells Using Multifunctional Gold Nanoprobe-Based Thermophoretic Assay.

Circulating tumor cells (CTCs) have emerged as powerful biomarkers for diagnosis of prostate cancer. However, the effective identification and concurrently accurate imaging of CTCs for early screening of prostate cancer have been rarely explored. Herein, we reported a multifunctional gold nanoprobe-based thermophoretic assay for simultaneous specific distinguishing of prostate cancer CTCs and sensitive imaging of intracellular microRNA (miR-21), achieving the rapid and precise detection of prostate cancer. The multifunctional gold nanoprobe (GNP-DNA/Ab) was modified by two types of prostate-specific antibodies, anti-PSMA and anti-EpCAM, which could effectively recognize the targeting CTCs, and meanwhile linked double-stranded DNA for further visually imaging intracellular miR-21. Upon the specific internalization of GNP-DNA/Ab by PC-3 cells, target aberrant miR-21 could displace the signal strand to recover the fluorescence signal for sensitive detection at the single-cell level, achieving single PC-3 cell imaging benefiting from the thermophoresis-mediated signal amplification procedure. Taking advantage of the sensitive miR-21 imaging performance, GNP-DNA/Ab could be employed to discriminate the PC-3 and Jurkat cells because of the different expression levels of miR-21. Notably, PC-3 cells were efficiently recognized from white blood cells, exhibiting promising potential for the early diagnosis of prostate cancer. Furthermore, GNP-DNA/Ab possessed good biocompatibility and stability. Therefore, this work provides a great tool for aberrant miRNA-related detection and specific discrimination of CTCs, achieving the early and accurate diagnosis of prostate cancer.

“All in one” nanoprobe Au-TTF-1 for target FL/CT bioimaging, machine learning technology and imaging-guided photothermal therapy against lung adenocarcinoma

The accurate preoperative diagnosis and tracking of lung adenocarcinoma is hindered by non-targeting and diffusion of dyes used for marking tumors. Hence, there is an urgent need to develop a practical nanoprobe for tracing lung adenocarcinoma precisely even treating them noninvasively. Herein, Gold nanoclusters (AuNCs) conjugate with thyroid transcription factor-1 (TTF-1) antibody, then multifunctional nanoprobe Au-TTF-1 is designed and synthesized, which underscores the paramount importance of advancing the machine learning diagnosis and bioimaging-guided treatment of lung adenocarcinoma. Bright fluorescence (FL) and strong CT signal of Au-TTF-1 set the stage for tracking. Furthermore, the high specificity of TTF-1 antibody facilitates selective targeting of lung adenocarcinoma cells as compared to common lung epithelial cells, so machine learning software Lung adenocarcinoma auxiliary detection system was designed, which combined with Au-TTF-1 to assist the intelligent recognition of lung adenocarcinoma jointly. Besides, Au-TTF-1 not only contributes to intuitive and targeted visualization, but also guides the following noninvasive photothermal treatment. The boundaries of tumor are light up by Au-TTF-1 for navigation, it penetrates into tumor and implements noninvasive photothermal treatment, resulting in ablating tumors in vivo locally. Above all, Au-TTF-1 serves as a key platform for target bio-imaging navigation, machine learning diagnosis and synergistic PTT as a single nanoprobe, which demonstrates attractive performance on lung adenocarcinoma.Graphical

Multifunctional dual-channel fluorescent nanoprobe for visual fluorescence detection of pathogenic bacteria and excessive antibiotics in food safety

With the rapid development of animal husbandry, animal food safety issues are increasingly exposed. Detecting pathogenic bacteria and residual antibiotics in animal food is of great significance for the early detection and regulation of harmful substances that threaten food safety. However, developing a fluorescent sensor that can detect both pathogenic bacteria and antibiotics is challenging. In this study, an interesting dual-channel ratiometric nanoprobe (CDs-Eu) based on europium-functionalized carbon dots was developed to realize the visual detection of Bacillus anthracis marker (DPA) and tetracycline antibiotics (TC) in a water environment under different excitation channels. This method had high sensitivity, comprehensive response range, anti-interference ability, and visualization for detecting DPA and TC. Combined with intelligent phone color scanning applications, a portable agarose gel nanosensor was designed to achieve multicolor on-site assessment of DPA and TC. In addition, an advanced three-to-six logic gate analysis method was also developed, which was expected to achieve intelligent sensing of DPA and TC in food safety.

Cell Membrane-Anchored SERS Biosensor for the Monitoring of Cell-Secreted MMP-9 during Cell-Cell Communication.

Matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme, degrades the extracellular matrix and plays a key role in cell communication. However, the real-time monitoring of cell-secreted MMP-9 during cell-cell communication remains a challenge. Herein, we developed a cell-based membrane-anchored surface-enhanced Raman scattering (SERS) biosensor using a Au@4-mercaptobenzonitrile (4-MBN) @Ag@peptide nanoprobe for the monitoring of cell-secreted MMP-9 during cell communication. The multifunctional nanoprobe was created with Au@4-MBN@Ag acting as an interference-free SERS substrate with high enhancement in which the peptide not only serves to anchor the cell membrane but also provides MMP-9-activatable cleaved peptide chains. MMP-9-mediated cleavage resulted in the detachment of the Au@4-MBN@Ag nanoparticles from the cell membrane, thereby decreasing the SERS signals of cancer cells. The cell membrane-anchored SERS biosensor enables the real-time monitoring of cell-secreted MMP-9 during the interaction of MCF-7 and HUVEC cells. This study successfully demonstrates the dynamic change of cell-secreted MMP-9 during the communication between MCF-7 cells and HUVEC cells. The proposed nanoprobe was also utilized to precisely evaluate the breast and hepatoma cancer cell aggressiveness. This study provides a novel strategy for real-time monitoring of MMP-9 secretion during cell communication, which is promising for the investigation of the mechanisms underlying different tumor processes.

Thirty years of research on photoacoustic imaging in the field of cancer: A scientometric analysis of hotspots, bursts, and research trends.

As a novel imaging modality based on photoacoustic effects, photoacoustic imaging (PAI) has shown great potential in biomedical applications, especially in the field of cancer. The purpose of our research was to identify collaborations between different institutions, authors, and countries, and to explore the hotspots and prospects of PAI research in the field of cancer. We downloaded publications on PAI research from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection database. Bibliometric analysis was performed using VOSviewer and CiteSpace software. A total of 2561 papers related to PAI research in the field of cancer were identified. A total of 10,105 authors participated in the PAI study, of which the majority (69.33%) authors participated in only 1 article. China (1638, 63.96%) was the country with the most articles in this field, and the Chinese Academy of Sciences (329, 12.85%) was the most productive institution. ACS Applied Materials & Interfaces (146, 5.70%) was the most productive journal and ACS Nano (7262 co-citations) was the most co-cited journal. Current hot topics of PAI research in the cancer field were the construction and development of multifunctional photoacoustic nanoprobes to achieve the integration of tumor detection and treatment. The application of photoacoustic imaging in the field of cancer is in the vigorous development stage and has a bright prospect. There was a wealth of cooperation between authors, countries, and institutions. Our findings can provide information about the future direction of funding agencies and research groups.

Tumor-targeted bioactive nanoprobes visualizing of hydrogen peroxide for forecasting chemotherapy-exacerbated malignant prognosis.

Introduction: Fluorescent visualization of hydrogen peroxide in the tumor microenvironment (TME) is conducive to predicting malignant prognosis after chemotherapy. Two photon microscopy has been employed for in vivo hydrogen peroxide detection owing to its advantages of deep penetration and low phototoxicity. Methods: In this study, a two-photon fluorescent probe (TPFP) was protected by mesoporous silica nanoparticles (MSNs) and masked by cloaking the cancer cell membranes (CM), forming a tumor-targeted bioactive nanoprobe, termed MSN@TPFP@CM. Results: This multifunctional nanoprobe allowed for the effective and selective detection of excessive hydrogen peroxide production in chemotherapeutic Etoposide (VP-16)-challenged tumor cells using two-photon microscopy. After specific accumulation in tumors, VP-16-MSN@TPFP@CM monitored tumor-specific hydrogen peroxide levels and revealed a positive correlation between oxidative stress in the TME and chemotherapy-exacerbated malignant prognosis. Discussion: Given the recent translation of fluorescent imaging into early clinical trials and the high biocompatibility of bioactive nanoprobes, our approach may pave the way for specific imaging of oxidative stress in solid tumors after treatment and provide a promising technology for malignant prognosis predictions.

Bioorthogonal Glycoengineering-Mediated Multifunctional Liquid Metal Nanoprobes for Highly Efficient Photoacoustic Imaging-Guided Photothermal/Chemotherapy of Tumor.

The development of a multifunctional cancer diagnosis and treatment platform offers excellent prospects for the effective eradication of malignant solid tumors. Herein, a doxorubicin hydrochloride (DOX)-loaded tannic acid (TA)-coated liquid metal (LM) multifunctional nanoprobe was synthesized and applied as a highly efficient platform for the photoacoustic (PA) imaging-guided photothermal/chemotherapy of tumor. The multifunctional nanoprobes exhibited strong near-infrared absorption, a remarkable photothermal conversion efficiency (PCE) of 55%, and high DOX loading capacity. Combined with the large intrinsic thermal expansion coefficient of LM, highly efficient PA imaging and effective drug release were realized. The LM-based multifunctional nanoprobes were specifically adsorbed into the cancer cells and tumor tissues via glycoengineering biorthogonal chemistry. The in vitro and in vivo photothermal/chemo-anticancer activity confirmed their promising potential in cancer treatment. The subcutaneous breast tumor-bearing mice completely recovered in 5 days under light illumination with clear PA imaging presentation, which showed better antitumor outcomes than single-mode chemotherapy or photothermal therapy (PTT), while keeping side effects at a minimum. Such an LM-based PA imaging-guided photothermal/chemotherapy strategy provided a valuable platform for resistant cancer precise treatment and intelligent biomedicine.

Metal-Organic Framework-Derived Multifunctional Nucleic Acid Nanoprobes for Hypoxia Imaging-Guided Radiosensitization.

The efficacy of radiotherapy (RT) is usually restricted by the hypoxic microenvironment and the poor radiation attenuation coefficient of tumor tissue. Theranostic probes that simultaneously evaluate the hypoxia degree and sensitize cancer cells toward RT are promising for improving the treatment efficacy and avoiding overtreatment. We rationally designed a metal-organic framework (MOF)-derived multifunctional nanoprobe for hypoxia imaging-guided radiosensitization. Hf-MOF was carbonized to obtain a porous carbonous nanostructure containing ultrasmall HfO2 (HfC); then, a fluorophore-labeled HIF-α mRNA antisense sequence was readily adsorbed and quenched by HfC to obtain the nanoprobe (termed HfC-Hy). The antisense sequence could easily hybridize with HIF-α mRNA and recover its fluorescence signal to evaluate the degree of hypoxia, while the HfC nanostructure could deposit more radiation energy in cancer cells for radiosensitization. A series of in vitro and in vivo experiments demonstrated that the nanoprobe could be successfully utilized for imaging the hypoxic degree of cancer cells/tumor tissue and guiding radiosensitization. This work not only developed a highly efficient and safe nanosensitizer but also offered a potential solution for customized clinical RT.

2-Methoxyestradiol loaded mesoporous polydopamine nanoprobes for hypoxia alleviation and sorafenib synergistic treatment of hepatocellular carcinoma

Hepatocellular carcinoma is a common and highly malignant disease. As a currently designated systemic chemotherapeutic agent for advanced Hepatocellular carcinoma, sorafenib has been confronted with dilemma of drug-resistance caused by tumor hypoxia, which hinders the therapeutic efficacy of the drug. Based on this, a multifunctional mesoporous polydopamine nanoprobe 2Me-SPIO-CY5.5@AAZ-MPDA with a mesoporous frame loaded 2-Methoxyestradiol, Superparamagnetic Iron Oxide Nanoparticles and the near-infrared dye cyanine 5.5, conjugated with hypoxia Hepatocellular carcinoma-specific targeting molecule of sulfonamides acetazolamide, is fabricated for hypoxic region targeting, sorafenib resistance reversion and photothermal therapy of Hepatocellular carcinoma. In addition, the magnetic resonance imaging/fluorescence/photoacoustic tri-modal imaging ability enables the tracing of the nanoprobes and monitoring the treatment procedure in vivo, providing a new methods of imaging-guided Hepatocellular carcinoma synergic treatment which improves the long-term therapeutic effects of sorafenib.

Multifunctional Nanoprobe-Amplified Enzyme-Linked Immunosorbent Assay on Capillary: A Universal Platform for Simple, Rapid, and Ultrasensitive Dual-Mode Pathogen Detection.

Although the traditional enzyme-linked immunosorbent assay (ELISA) has been widely applied in pathogen detection and clinical diagnostics, it always suffers from complex procedures, a long incubation time, unsatisfying sensitivity, and a single signal readout. Here, we developed a simple, rapid, and ultrasensitive platform for dual-mode pathogen detection based on a multifunctional nanoprobe integrated with a capillary ELISA (CLISA) platform. The novel capture antibodies-modified capillaries can act as a swab to combine in situ trace sampling and detection procedures, eliminating the dissociation between sampling and detection in traditional ELISA assays. With excellent photothermal and peroxidase-like activity, the Fe3O4@MoS2 nanoprobe with a unique p-n heterojunction was chosen as an enzyme substitute and amplified signal tag to label the detection antibody for further sandwich immune sensing. As the analyte concentration increased, the Fe3O4@MoS2 probe could generate dual-mode signals, including remarkable color changes from the chromogenic substrate oxidation as well as photothermal enhancement. Moreover, to avoid false negative results, the excellent magnetic capability of the Fe3O4@MoS2 probe can be used to pre-enrich the trace analytes, amplifying the detection signal and enhancing the immunoassay's sensitivity. Under optimal conditions, specific and rapid detection of SARS-CoV-2 has been realized successfully based on this integrated nanoprobe-enhanced CLISA platform. The detection limits were 5.41 pg·mL-1 for the photothermal assay and 150 pg·mL-1 for the visual colorimetric assay. More importantly, the simple, affordable, and portable platform can also be expanded to rapidly detect other targets such as Staphylococcus aureus and Salmonella typhimurium in practical samples, making it a universal and attractive tool for multiple pathogen analysis and clinical testing in the post COVID-19 era.