Case report: Leptomeningeal metastasis of advanced nasopharyngeal carcinoma treated with chemoimmunotherapy.

Leptomeningeal metastasis (LM) of nasopharyngeal carcinoma (NPC) is rare and associated with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been the standard first-line treatment for metastatic NPC, but their effect on meningeal metastasis of NPC needs further investigation. A 38-year-old man complained of bilateral neck masses and sought medical care. He was diagnosed with nasopharyngeal undifferentiated non-keratinizing carcinoma with bilateral cervical lymph node metastasis and multiple bone metastasis, stage cT4N2M1 IVb. Then, the patient received first-line anti-PD-1 antibody tislelizumab combined with gemcitabine and cisplatin and achieved partial response. After seven cycles of first-line chemoimmunotherapy, the patient subsequently developed neurological symptoms, including unsteady walking, slurred speech, coughing on drinking, and unconsciousness. MRI showed leptomeningeal linear enhancement, and cerebrospinal fluid (CSF) analysis indicated Epstein-Barr virus (EBV) infection and squamous cell carcinoma cytology, suggesting the diagnosis of leptomeningeal metastasis. After the definite diagnosis of LM, the patient's condition deteriorated rapidly, leading to his death from brain herniation. We reported the first case of advanced NPC with pathologically confirmed leptomeningeal metastasis after receiving first-line chemoimmunotherapy. Considering the poor prognosis of LM, it is suggested to perform MRI and CSF examination when patients have neurological symptoms. Although immunotherapy significantly improved survival outcomes of advanced NPC patients, it seemed not effective in the setting of LM. The effect of other treatment options, such as radiation therapy and intrathecal therapy, requires further verification.

The maximum tumor growth rate predicts clinical outcomes of patients with small-cell lung cancer undergoing first-line chemotherapy plus immune-checkpoint inhibitor therapy.

BACKGROUND: Currently, no biomarkers can accurately predict survival outcomes in patients with SCLC undergoing treatment. Tumor growth rate (TGR; percent size change per month [%/m]) is suggested as an imaging predictor of response to anti-cancer treatment. We aimed to evaluate the predictive role of the maximum TGR (TGRmax) for outcomes of small-cell lung cancer (SCLC) patients undergoing first-line chemotherapy plus immune-checkpoint inhibitor (ICI) treatment. METHODS: Patients with SCLC receiving first-line chemotherapy plus immunotherapy were analyzed within this retrospective study. The X-tile program was used to identify the cut-off value of TGRmax based on maximum progression-free survival (PFS) stratification. The Kaplan-Meier methods and Cox regression models were used to evaluate the effect of the presence of TGRmax on PFS and overall survival (OS). RESULTS: In total, 104 patients were evaluated. Median (range) TGRmax was -33.9 (-65.2 to 21.6) %/m and the optimal cut-off value of TGRmax was -34.3%/m. Multivariate Cox regression analysis revealed that patients with TGRmax > -34.3%/m was associated with shorter PFS (hazard ratio [HR], 2.81; 95% CI, 1.71-4.63; p < 0.001) and OS (HR, 3.17; 95% CI, 1.41-7.08; p = 0.005). In patients who received partial response (PR), Kaplan-Meier survival analyses showed that superior PFS and OS (p = 0.005 and p = 0.009, respectively) benefit was observed when TGRmax ≤-34.3%/m. CONCLUSIONS: SCLC patients with TGRmax > -34.3%/m had worse PFS and OS in first-line ICI plus platin-based chemotherapy. TGRmax could independently serve as an early biomarker to predict the benefit from chemoimmunotherapy.

Simplified one-pot 18F-labeling of biomolecules with in situ generated fluorothiophosphate synthons in high molar activity.

Rationale: Conventional 18F-labeling methods that demand substrate pre-modification or lengthy radiosynthesis procedures have impeded the visualization and translation of numerous biomolecules, as biomarkers or ligands, using modern positron emission tomography techniques in vivo. Moreover, 18F-labeled biomolecules in high molar activity (Am) that are indispensable for sensitive imaging could be only achieved under strict labeling conditions. Methods: Herein, 18F-labeled fluorothiophosphate (FTP) synthons in high Am have been generated rapidly in situ in reaction solutions with < 5% water via nucleophilic substitution by wet [18F]F-, which required minimal processing from cyclotron target water. Results: Various 18F-labeled FTP synthons have been prepared in 30 sec at room temperature with high radiochemical yields > 75% (isolated, non-decay-corrected). FTP synthons with unsaturated hydrocarbon or activated ester group can conjugate with typical small molecules, peptides, proteins, and metallic nanoparticles. 337-517 GBq µmol-1 Am has been achieved for 18F-labeled c(RGDyK) peptide using an automatic module with 37-74 GBq initial activity. Conclusion: The combination of high 18F-fluorination efficiency of FTP synthons and following mild conjugation condition provides a universal simplified one-pot 18F-labeling method for broad unmodified biomolecular substrates.

A neglected cervicovesical fistula diagnosed and repaired by combined hysteroscopy and laparoscopy: A case report and review of literature.

Objective: To analyze a case of neglected cervicovesical fistula with intrauterine adhesions caused by cesarean section. Methods: A 36-year-old female patient with a history of two previous cesarean sections complained of the absence of menstruation for the last 18 months. The diagnosis of the cervicovesical fistula was made through hysteroscopy and cystoscopy. The reconstruction of the uterus and bladder was achieved by a laparoscopic repair technique. Results: The patient resumed normal menstruation postoperatively without complaining of any complications. Uterine continuity and cavity had been restored to normal at the second look of hysteroscopy. Conclusions: Cervicovesical fistula with intrauterine adhesions is very rare in our clinical work. Hysteroscopy might play an essential role in diagnosing cervicovesical fistula and IUA. In our literature review, a surgical approach was the mainstay and definitive management of the cervicovesical fistula following a cesarean section.

Keratin 80 Promotes Migration and Invasion of Non-Small Cell Lung Cancer Cells by Regulating the TGF-ß/SMAD Pathway.

Upregulation of keratin 80 (KRT80) expression levels and carcinogenic function has been found in several types of tumors. However, its contribution and mechanism in NSCLC remain to be outlined. In this study, bioinformatic investigation from the TCGA dataset revealed that KRT80 was confirmed to be elevated in human NSCLC tissues. The results of qRT-PCR and Western blot assays disclosed that KRT80 was uplifted in NSCLC cells. Data from CCK-8 and colony formation assays exhibited that depletion of KRT80 restrained NSCLC cell proliferation. Findings from Transwell and Western blot assays illustrated that downregulation of KRT80 inhibited NSCLC cell migration, invasion, and EMT. Further mechanism exploration implied that KRT80 may be included within the regulation of EMT of NSCLC cells by affecting the TGF-ß/SMAD pathway. Moreover, depletion of KRT80 attenuated xenograft tumor growth and the expressions of KRT80, Ki-67, and TGFBR1. In conclusion, depletion of KRT80 repressed NSCLC cell proliferation, invasion, and EMT, possibly mediated by the TGF-ß/SMAD signaling pathway, indicating that KRT80 may be a potentially useful target for NSCLC.

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4.

Background: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). Methods: QRT-PCR was employed to assess the expression of TP73-AS1, miR-125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. Results: Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued-function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. Conclusion: The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future.

Tumor-Microenvironment-Responsive Biodegradable Nanoagents Based on Lanthanide Nucleotide Self-Assemblies toward Precise Cancer Therapy.

Stimuli-responsive nanoagents, which simultaneously satisfy normal tissue clearance and tumor-specific responsive treatment, are highly attractive for precise cancer theranostics. Herein, we develop a unique template-induced self-assembly strategy for the exquisitely controlled synthesis of self-assembled lanthanide (Ln3+ ) nucleotide nanoparticles (LNNPs) with amorphous structure and tunable size from sub-5 nm to 105 nm. By virtue of the low-temperature (10 K) and high-resolution spectroscopy, the local site symmetry of Ln3+ in LNNPs is unraveled for the first time. The proposed LNNPs are further demonstrated to possess the ability for highly efficient loading and tumor-microenvironment-responsive release of doxorubicin. Particularly, sub-5 nm LNNPs not only exhibit excellent biocompatibility and predominant renal-clearance performance, but also enable efficient tumor retention. These findings reveal the great potential of LNNPs as a new generation of therapeutic platform to overcome the dilemma between efficient therapy and long-term toxicity of nanoagents for future clinical applications.

Development of Rofecoxib-Based Fluorescent Probes and Investigations on Their Solvatochromism, AIE Activity, Mechanochromism, and COX-2-Targeted Bioimaging.

Cyclooxygenase-2 (COX-2) fluorescent probes are promising tools for early diagnosis of cancer. Traditionally, COX-2 probes were designed by connecting two parts, a fluorophore and a COX-2 binding unit, via a flexible linker. Herein, a new class of COX-2-specific fluorescent probes have been developed via one-step modification from rofecoxib by an integrative approach to combine the binding unit and the fluorophore into one. Among them, several new rofecoxib analogues not only exhibited still potent COX-2 binding ability but also exhibited attractive fluorescence properties, such as tunable blue-red emission, solvatochromism, aggression-induced emission behavior, and mechanochromism. Notably, the emission of 2a16 can be switched between green-yellow in the crystalline state and red-orange in the amorphous state by grinding and fuming treatments. Furthermore, the highly fluorescent compound 2a16 (Φf = 0.94 in powder) displayed a much stronger fluorescence imaging of COX-2 in HeLa cancer cells overexpressing COX-2 than RAW264.7 normal cells with a minimal expression of COX-2. Most importantly, 2a16 can light up human cancer tissues from adjacent normal tissues with a much brighter fluorescence by targeting the COX-2 enzyme. These results demonstrated the potential of 2a16 as a new red fluorescent probe for human cancer imaging in clinical applications.

The prognostic value of inflammation markers in postoperative gliomas with or without adjuvant treatments.

ABSTRACT: Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 109/L, 2.9 × 109/L, and 123.2 × 109/L, respectively. Patients who are pre-SII < 781.5 × 109/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 109/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000-1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973-0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979-1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.

Ultrasensitive Point-of-Care Test for Tumor Marker in Human Saliva Based on Luminescence-Amplification Strategy of Lanthanide Nanoprobes.

The point-of-care detection of tumor markers in saliva with high sensitivity and specificity remains a daunting challenge in biomedical research and clinical applications. Herein, a facile and ultrasensitive detection of tumor marker in saliva based on luminescence-amplification strategy of lanthanide nanoprobes is proposed. Eu2O3 nanocrystals are employed as bioprobes, which can be easily dissolved in acidic enhancer solution and transform into a large number of highly luminescent Eu3+ micelles. Meanwhile, disposable syringe filter equipped with nitrocellulose membrane is used as bioassay platform, which facilitates the accomplishment of detection process within 10 min. The rational integration of dissolution enhanced luminescent bioassay strategy and miniaturized detection device enables the unique lab-in-syringe assay of tumor marker like carcinoembryonic antigen (CEA, an important tumor marker in clinic diagnosis and prognosis of cancer) with a detection limit down to 1.47 pg mL-1 (7.35 × 10-15 m). Upon illumination with a portable UV flashlight, the photoluminescence intensity change above 0.1 ng mL-1 (0.5 × 10-12 m) of CEA can be visually detected by naked eyes, which allows one to qualitatively evaluate the CEA level. Moreover, we confirm the reliability of using the amplified luminescence of Eu2O3 nanoprobes for direct quantitation of CEA in patient saliva samples, thus validates the practicality of the proposed strategy for both clinical diagnosis and home self-monitoring of tumor marker in human saliva.

Structure and Oxidation Effects on Conformation and Thermoresponsiveness of the OEGylated Poly(glutamic acid)-Bearing Side-Chain Thioether Linkers.

A series of side-chain thioether-linked OEGylated poly(glutamic acid) (PGAs) have been synthesized by "thiol-ene" synthetic methodology, where both the oligo-ethylene glycol (OEG) length and the hydrophobic linkers at the side chains are varied to learn how these structural features affect the secondary structure and thermoresponsive behaviors in water. Before side-chain oxidation, the structural factors affecting the α-helicity include the backbone length, the OEG length, and the hydrophobic linkers' length at the side chains; however, the OEG length plays the most crucial role among these factors because longer OEG around the peripheral side chains can stop water penetration into the backbone to disturb the intramolecular H bonds, which finally allows stabilizing the α-helix; after the oxidation, the polypeptides show increased α-helicity because of the enhanced hydrophilicity. More interestingly, a rare oxidation-induced conformation transition from the ordered ß-sheet to the ordered α-helix can be achieved. In addition, only the OEGylated poly(glutamic acids) (PGAs) with shorter hydrophobic linkers and longer OEG can display the thermoresponsive properties before the oxidation but the subsequent oxidation can cause the polypeptides bearing longer hydrophobic linkers to exhibit the thermosensitivity since sulfone formation at the side chain can lead to final hydrophilicity-hydrophobicity balance. This work is meaningful to understand the secondary structure-associated solution behaviors of the synthetic polypeptides.

One-Step Transformation from Rofecoxib to a COX-2 NIR Probe for Human Cancer Tissue/Organoid Targeted Bioimaging.

COX-2 fluorescent probes are promising tools for cancer diagnosis. Such probes have been conventionally designed by conjugating a fluorophore to COX-2 inhibitors through lengthy synthetic processes. Herein, a type of fluorescent probe for COX-2 imaging has been developed using a single-step process from rofecoxib. In total, six rofecoxib analogues were designed using this unique strategy. Several analogues retained comparative COX-2 targeting activity of rofecoxib and also exhibited attractive fluorescent properties, which were investigated using a combination of experimental and theoretical approaches. The most potent analogue, 2a1, displayed strong fluorescent imaging of COX-2 in HeLa cells overexpressing COX-2 compared to Raw 264.7 cells and celecoxib-treated HeLa cells that expressed low levels of COX-2. Notably, our studies indicate that 2a1 can differentiate human cancer tissue from adjacent tissue with much brighter fluorescence either in histological section or cultured 3D organoids. These results illustrate the potential of 2a1 as a COX-2 near infrared fluorescent probe for human cancer imaging in clinical settings.

A New Class of NIR-II Gold Nanocluster-Based Protein Biolabels for In†Vivo Tumor-Targeted Imaging.

The design of bright NIR-II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient strategy to synthesize bright NIR-II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (<2 nm) and strong macrocycle-based host-guest chemistry, the as-synthesized CD-Au NCs can readily label proteins/antibodies. Moreover, the labelled proteins/antibodies enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor-targeted imaging. CD-Au NCs are stable in the harsh biological environment and show good biocompatibility and high renal clearance efficiency. Therefore, the NIR-II biolabels developed in this study provide a promising platform to monitor the physiological behavior of biomolecules in living organisms.

Design and Synthesis of Biotinylated Bivalent Carboline Derivatives as Potent Antitumor Agents.

Compound 6, a novel ß-carboline comprising two 1-methyl-9H-ß-carboline-3-carboxylic acids and a biotin moiety conjugated together using tris(2-aminoethyl)amine, was synthesized and tested for its cytotoxicity toward MCF-7 and HepG2 cell lines and antitumor potency in an S180 tumor-bearing mouse model. Compound 6 was delivered via biotin receptor-mediated endocytosis and exerted its therapeutic effects by intercalation binding with DNA. In vivo antitumor evaluations of 6 revealed that it is efficacious and exhibits low systemic toxicity.

Near-infrared-excited upconversion photodynamic therapy of extensively drug-resistant Acinetobacter baumannii based on lanthanide nanoparticles.

Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 µg mL-1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm-2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.

Theranostic nanobubble encapsulating a plasmon-enhanced upconversion hybrid nanosystem for cancer therapy.

Nanobubble (NB), which simultaneously enhances ultrasound (US) images and access therapeutic platforms, is required for future cancer treatment. Methods: We designed a theranostic agent for novel cancer treatment by using an NB-encapsulated hybrid nanosystem that can be monitored by US and fluorescent imaging and activated by near-infrared (NIR) light. The nanosystem was transported to the tumor through the enhanced permeability and retention effect. The hybrid nanosystem comprised upconversion nanoparticle (UCNP) and mesoporous silica-coated gold nanorod (AuNR@mS) with the photosensitizer merocyanine 540 to realize dual phototherapy. Results: With the NIR light-triggered, the luminous intensity of the UCNP was enhanced by doping holmium ion and emitted visible green and red lights at 540 and 660 nm. The high optical density state between the UCNP and AuNR@mS can induce plasmonic enhancement to improve the photothermal and photodynamic effects, resulting in cell death by apoptosis. The nanosystem showed excellent stability to avoid the aggregation of nanoparticles during the treatment. JC-1 dye was used as an indicator of mitochondrial membrane potential to identify the mechanism of cell death. The results of in vitro and in vivo analyses confirmed the curative effect of improved dual phototherapy. Conclusion: We developed and showed the therapeutic functions of a novel nanosystem with the combination of multiple theranostic nanoplatforms that can be triggered and activated by 808 nm NIR laser and US.

Lanthanide Metal-Organic Framework Nanoprobes for the In Vitro Detection of Cardiac Disease Markers.

Acute myocardial infarction (AMI) is one of the leading causes of death around the world. An early and accurate diagnosis of AMI is critical to reduce the mortality rate. As an important cardiac biomarker, creatine kinase (CK) has been used in the clinical diagnosis of AMI. However, it still remains a great challenge to realize highly sensitive and selective CK detection in blood specimens. Herein, we have developed an ultrasensitive platform for the detection of CK activity based on time-resolved (TR) luminescent lanthanide metal-organic framework nanoprobes (Eu-QPTCA). Benefiting from the intense emission of lanthanide ions sensitized by the organic ligands and the eliminated short-lived autofluorescence by the TR technique, these nanoprobes enabled the homogeneous detection of CK activity with a limit of detection down to 1.0 U/L, which is about 1 order of magnitude improvement relative to that of the traditional methods. In addition, the Eu-QPTCA nanoprobes showed superior selectivity and reliability toward the practical detection of CK activity in human serum, indicating the great significance of our method in the early diagnosis of AMI. We envision that the proposed bioassay strategy can be extended to the detection of other phosphorylation enzymes, paving a way for promising applications in clinical diagnostics.

A Strategy of NIR Dual-Excitation Upconversion for Ratiometric Intracellular Detection.

Intracellular detection is highly desirable for biological research and clinical diagnosis, yet its quantitative analysis with noninvasivity, sensitivity, and accuracy remains challenging. Herein, a near-infrared (NIR) dual-excitation strategy is reported for ratiometric intracellular detection through the design of dye-sensitized upconversion probes and employment of a purpose-built NIR dual-laser confocal microscope. NIR dye IR808, a recognizer of intracellular analyte hypochlorite, is introduced as energy donor and Yb,Er-doped NaGdF4 upconversion nanoparticles are adopted as energy acceptor in the as-designed nanoprobes. The efficient analyte-dependent energy transfer and low background luminescence endow the nanoprobes with ultrahigh sensitivity. In addition, with the nonanalyte-dependent upconversion luminescence (UCL) excited by 980 nm as a self-calibrated signal, the interference from environmental fluctuation can be alleviated. Furthermore, the dual 808/980 nm excited ratiometric UCL is demonstrated for the quantification of the level of intracellular hypochlorite. Particularly, the intrinsic hypochlorite with only nanomolar concentration in live MCF-7 cells in the absence of exogenous stimuli is determined. Such an NIR dual-excitation ratiometric strategy based on dye-sensitized UCL probes can be easily extended to detect various intracellular analytes through tailoring the reactive NIR dyes, which provides a promising tool for probing biochemical processes in live cells and diagnosing diseases.

Graphene-Oxide-Modified Lanthanide Nanoprobes for Tumor-Targeted Visible/NIR-II Luminescence Imaging.

The synthesis of hydrophilic lanthanide-doped nanocrystals (Ln3+ -NCs) with molecular recognition ability for bioimaging currently remains a challenge. Herein, we present an effective strategy to circumvent this bottleneck by encapsulating Ln3+ -NCs in graphene oxide (NCs@GO). Monodisperse NCs@GO was prepared by optimizing GO size and core-shell structure of NaYF4 :Yb,Er@NaYF4 , thus combining the intense visible/near-infrared II (NIR-II) luminescence of NCs and the unique surface properties and biomedical functions of GO. Such nanostructures not only feature broad solvent dispersibility, efficient cell uptake, and excellent biocompatibility but also enable further modifications with various agents such as DNA, proteins, or nanoparticles without tedious procedures. Moreover, we demonstrate in proof-of-concept experiments that NCs@GO can realize simultaneous intracellular tracking and microRNA-21 visualization, as well as highly sensitive in vivo tumor-targeted NIR-II imaging at 1525 nm.

Broadband NIR photostimulated luminescence nanoprobes based on CaS:Eu2+,Sm3+ nanocrystals.

Near-infrared (NIR) photostimulated luminescence (PSL) nanocrystals (NCs) have recently evoked considerable interest in the field of biomedicine, but are currently limited by the controlled synthesis of efficient PSL NCs. Herein, we report for the first time the controlled synthesis of CaS:Eu2+,Sm3+ NIR PSL NCs through a high-temperature co-precipitation method. The role of Sm3+ co-doping and the effect of thermal annealing on the optical properties of the NCs as well as the charging and discharging processes, the trap depth distribution, and the underlying PSL mechanism are comprehensively surveyed by means of photoluminescence, persistent luminescence, thermoluminescence, and PSL spectroscopies. The as-prepared NCs exhibit intense PSL of Eu2+ at 650 nm with a fast response to stimulation in a broad NIR region from 800 nm to 1600 nm, a duration time longer than 2 h, and an extremely low power density threshold down to 10 mW cm-2 at 980 nm. Furthermore, by taking advantage of the intense NIR PSL, we demonstrate the application of CaS:Eu2+,Sm3+ NCs as sensitive luminescent nanoprobes for biotin receptor-targeted cancer cell imaging. These results reveal the great promise of CaS:Eu2+,Sm3+ nanoprobes for autofluorescence-free bioimaging, and also lay the foundation for future design of efficient NIR PSL nanoprobes towards versatile bioapplications.