Imaging and Downstaging Bladder Cancer with the 177Lu-Labeled Bioorthogonal Nanoprobe.

Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

DFT Study of Metal (Ag, Au, Pt)-Modified SnS2 for Adsorption of SF6 Decomposition Gases in Gas-Insulated Switchgear.

In this study, the gas-sensitive response of metal (Ag, Au, Pt)-modified SnS2 toward SF6 decomposition gases (SOF2, SO2F2, SO2, H2S) in gas-insulated switchgear was studied by analyzing the adsorption structure, band structure, charge transfer, and density of states based on density functional theory. The results show that the adsorption of the four target gases on pristine SnS2 belongs to weak physical adsorption. Compared with the pristine SnS2, the adsorption energy of the transition metal atom-modified SnS2 monolayer has been improved to a certain extent and the adsorption capacity of these four gases on the transition metal atom-modified SnS2 monolayer has obviously improved. Moreover, the recovery time of Ag-SnS2/SOF2, Ag-SnS2/SO2F2, Au-SnS2/SOF2, Au-SnS2/SO2F2, and Pt-SnS2/SO2F2 is too short, indicating that these conditions have poor adsorption capacity and sensitivity to SF6 decomposition gases and are not suitable as detection materials for these gases. According to the different changes in conductivity during adsorption, it provides a feasible solution to detect each SF6 decomposition gas. This theoretical study effectively explained the adsorption and sensing properties between the metal-modified monolayers and gases.

Unveiling the Biologically Dynamic Degradation of Iron Oxide Nanoparticles via a Continuous Flow System.

Nanomaterials are increasingly being employed for biomedical applications, necessitating a comprehensive understanding of their degradation behavior and potential toxicity in the biological environment. This study utilizes a continuous flow system to simulate the biologically relevant degradation conditions and investigate the effects of pH, protein, redox species, and chelation ligand on the degradation of iron oxide nanoparticles. The morphology, aggregation state, and relaxivity of iron oxide nanoparticles after degradation are systematically characterized. The results reveal that the iron oxide nanoparticles degrade at a significantly higher rate under the acidic environment. Moreover, incubation with bovine serum albumin enhances the stability and decreases the dissolution rate of iron oxide nanoparticles. In contrast, glutathione accelerates the degradation of iron oxide nanoparticles, while the presence of sodium citrate leads to the fastest degradation. This study reveals that iron oxide nanoparticles undergo degradation through various mechanisms in different biological microenvironments. Furthermore, the dissolution and aggregation of iron oxide nanoparticles during degradation significantly impact their relaxivity, which has implications for their efficacy as magnetic resonance imaging contrast agents in vivo. The results provide valuable insights for assessing biosafety and bridge the gap between fundamental research and clinical applications of iron oxide nanoparticles.

Radiotherapy-Triggered In Situ Tumor Vaccination Boosts Checkpoint Blockaded Immune Response via Antigen-Capturing Nanoadjuvants.

In situ vaccination (ISV) formed with the aid of intratumorally injected adjuvants has shed bright light on enhancing the abscopal therapeutic effects of radiotherapy. However, the limited availability of antigens resulting from the radiotherapy-induced immunogenic cell death largely hampers the clinical outcome of ISV. To maximally utilize the radiotherapy-induced antigen, we herein developed a strategy by capturing the radiotherapy-induced antigen in situ with a nanoadjuvant comprised of CpG-loaded Fe3O4 nanoparticles. The highly efficient click reaction between the maleimide residue on the nanoadjuvant and sulfhydryl group on the antigen maximized the bioavailability of autoantigens and CpG adjuvant in vivo. Importantly, combined immune checkpoint blockade can reverse T cell exhaustion after treatment with radiotherapy-induced ISV, thereby largely suppressing the treated and distant tumor. Mechanistically, metabolomics reveals the intratumorally injected nanoadjuvants disrupt redox homeostasis in the tumor microenvironment, further inducing tumor ferroptosis after radiotherapy. Overall, the current study highlights the immense potential of the innovative antigen-capturing nanoadjuvants for synergistically enhancing the antitumor effect.

In vivo clinical molecular imaging of T cell activity.

Tumor immunotherapy is refashioning traditional treatments in the clinic for certain tumors, especially by relying on the activation of T cells. However, the safety and effectiveness of many antitumor immunotherapeutic agents are suboptimal due to difficulties encountered in assessing T cell responses and adjusting treatment regimens accordingly. Here, we review advances in the clinical visualization of T cell activity in vivo, and focus particularly on molecular imaging probes and biomarkers of T cell activation. Current challenges and prospects are also discussed that aim to achieve a better strategy for real-time monitoring of T cell activity, predicting prognoses and responses to tumor immunotherapy, and assessing disease management.

Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.

The extracellular signal-regulated kinase 5 (Erk5) signaling plays a crucial role in cancer, and regulating its activity may have potential in cancer chemotherapy. In this study, a series of novel 7-azaindole derivatives (4a-5o) were designed and synthesized. Their antitumor activities on human lung cancer A549 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining and colony formation assay. Among them, compounds 4a, 4 h, 5d and 5j exhibited good anti-proliferative activity with the IC50 values of 6.23 µg/mL, 8.52 µg/mL, 7.33 µg/mL and 4.56 µg/mL, respectively, equivalent to Erk5 positive control XMD8-92 (IC50 = 5.36 µg/mL). The results of structure-activity relationships (SAR) showed that double bond on the piperidine ring and N atoms at the N7 position of 7-azaindole was essential for their antiproliferative activity. Furthermore, compounds 4a and 5j exhibited good inhibition on Erk5 kinase through Western blot analysis and possible action site of compounds with Erk5 kinase was elucidated by molecular docking.

Exploring atherosclerosis imaging with contrast-enhanced MRI using PEGylated ultrasmall iron oxide nanoparticles.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.

Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro-photoacoustic dual-modality imaging probe comprising a near-infrared dye caged by a cathepsin K (CTSK)-cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near-infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep-seated early osteolytic metastases.

[Segmentation of prostate region in magnetic resonance images based on improved V-Net].

Magnetic resonance (MR) imaging is an important tool for prostate cancer diagnosis, and accurate segmentation of MR prostate regions by computer-aided diagnostic techniques is important for the diagnosis of prostate cancer. In this paper, we propose an improved end-to-end three-dimensional image segmentation network using a deep learning approach to the traditional V-Net network (V-Net) network in order to provide more accurate image segmentation results. Firstly, we fused the soft attention mechanism into the traditional V-Net's jump connection, and combined short jump connection and small convolutional kernel to further improve the network segmentation accuracy. Then the prostate region was segmented using the Prostate MR Image Segmentation 2012 (PROMISE 12) challenge dataset, and the model was evaluated using the dice similarity coefficient (DSC) and Hausdorff distance (HD). The DSC and HD values of the segmented model could reach 0.903 and 3.912 mm, respectively. The experimental results show that the algorithm in this paper can provide more accurate three-dimensional segmentation results, which can accurately and efficiently segment prostate MR images and provide a reliable basis for clinical diagnosis and treatment.

Biomimetic Upconversion Nanoplatform Synergizes Photodynamic Therapy and Enhanced Radiotherapy against Tumor Metastasis.

The easy recurrence and high metastasis of fatal tumors require the development of a combination therapy, which is able to overcome the drawbacks of monomodal strategies such as surgery, photodynamic therapy (PDT), and radiotherapy (RT). Taking the complementary advantages of PDT and RT, we present herein the integration of lanthanide-doped upconversion nanoparticles (UCNPs) with chlorin e6 (Ce6)-imbedded RBC membrane vesicles as a near-infrared-induced PDT agent for achieving synchronous depth PDT and RT with reduced radiation exposure. In such a nanoagent, gadolinium-doped UCNPs with strong X-ray attenuation ability act not only as a light transductor to activate the loaded photosensitizer Ce6 to allow PDT but also as a radiosensitizer to enhance RT. PDT with enhanced low-dose RT can achieve synergistic inhibition of tumor growth by producing reactive oxygen species to destroy local tumor cells and inducing strong T-cell-dependent immunogenic cell death to arrest systemic cancer metastasis. This combination of PDT and RT might be a potential appealing strategy for tumor eradication.

Reversing Acute Kidney Injury through Coordinated Interplay of Anti-Inflammation and Iron Supplementation.

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD+ ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, herein, an ultrasmall Fe3 O4 nanoparticle is used as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD+ . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe3 O4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD+ precursor into renal cells through nicotinamide riboside kinase 1 on the cell membrane. It is demonstrated that NMN-loaded Fe3 O4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicate that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti-ROS (reactive oxygen species), anti-inflammation, or even iron elimination.

A Tumor-Microenvironment-Activatable Molecular Pro-Theranostic Agent for Photodynamic and Immunotherapy of Cancer.

Cancer-associated fibroblasts (CAFs) are the major components of the tumor-associated matrix and play an important role in tumor progression and immunosuppression. Therefore, precise theranostics of CAFs are beneficial for CAFs-targeted therapies. However, imaging agents enabling precise theranostics of CAFs have been rarely exploited. To tackle this issue, a molecular pro-theranostic probe (FMP) with activatable fluorescence, photoacoustic (PA) imaging, and photodynamic therapy (PDT) is developed in response to fibroblast activation protein α (FAPα) overexpressed in >90% types of CAFs and some tumor cells. Attributed to efficient activatable phototoxicity toward CAFs and tumor cells, together with activated immunogenic cell death (ICD), complete tumor regression of primary tumors and abscopal effect of distant tumors are observed in a 4T1-tumor-bearing mice model. By integration with PD-L1 checkpoint blockade immunotherapy, enhanced systemic immune responses are evoked to obtain long-lasting tumor suppression of both primary and distant tumors as well as arrest systemic cancer metastasis in living mice.

Targeting STING Activation by Antigen-Inspired MnO2 Nanovaccines Optimizes Tumor Radiotherapy.

Immune checkpoint blockers therapy can improve the radiotherapy-induced immunosuppression by enhancing interferon secretion, but still suffer from low clinical response rate and potential adverse effects. Mn2+ -mediated activation of interferon gene stimulator (STING) pathway provides an alternative for combination radioimmunotherapy of tumor. However, it is still a challenge for specific delivery of Mn2+ to innate immune cells and targeting activation of STING pathway. Herein, a novel antigen-inspired MnO2 nanovaccine is fabricated as Mn2+ source and functionalized with mannose, enabling it to target innate immune cells to activate the STING pathway. Meanwhile, the release of Mn2+ in the intracellular lysosomes can also be for magnetic resonance imaging to monitor the dynamic distribution of nanovaccines in vivo. The targeting activation of STING pathway can enhance radiotherapy-induced immune responses for inhibiting local and distant tumors, and resisting tumor metastasis. The study proposes an optimized radiotherapy strategy through targeting STING activation of antigen-inspired nanovaccines.

Chemotherapy-Sensitized In Situ Vaccination for Malignant Osteosarcoma Enabled by Bioinspired Calcium Phosphonate Nanoagents.

How to effectively treat malignant osteosarcoma remains clinically challenging. Programmed delivery of chemotherapeutic agents and immunostimulants may offer a universal strategy for killing osteosarcoma cells while simultaneously eliciting in situ antitumor immunity. However, targeted chemoimmunotherapy lacks a reliable delivery system. To address this issue, we herein developed a bioinspired calcium phosphonate nanoagent that was synthesized by chemical reactions between Ca2+ and phosphonate residue from zoledronic acid using bovine serum albumin as a scaffold. In addition, methotrexate combination with a phosphorothioate CpG immunomodulator was also loaded for pH-responsive delivery to enable synergistic chemoimmunotherapy of osteosarcoma. The calcium phosphonate nanoagents were found to effectively accumulate in osteosarcoma for nearly 1 week, which is favorable for exerting the vaccination effects in situ by maturing dendritic cells and priming CD8+ T cells to suppress the osteosarcoma progression and pulmonary metastasis through controlled release of the three loaded agents in the acidic tumor microenvironment. The current study may thus offer a reliable delivery platform for achieving targeted chemotherapy-induced in situ antitumor immunity.

Polydopamine-Coated Radiolabeled Microspheres for Combinatorial Radioembolization and Photothermal Cancer Therapy.

Transarterial radioembolization (TARE) is a local radionuclide therapy and is successfully used in hepatocellular carcinoma (HCC) treatment. Radioactive microspheres have been widely studied for TARE. Preparation of ideal radioactive microspheres is significant for clinical research and patient treatment. In this study, we have designed a novel multifunctional microsphere, i.e., polydopamine (PDA)-coated 177Lu-radiolabeled silica microspheres (MS) denoted as 177Lu-MS@PDA, which can be used for TARE and photothermal therapy (PTT). The radiostability of 177Lu-MS@PDA was significantly improved by coating 177Lu-MS with PDA. In addition, the coating of PDA makes microspheres have excellent photothermal performance. MicroSPECT/CT images showed that 177Lu-MS@PDA was accurately embolized and remained in the tumor during the observation time. At the time, it also showed that 177Lu-MS@PDA was very stable in vivo. Furthermore, the anti-tumor results demonstrated that TARE combined with PTT of 177Lu-MS@PDA can significantly inhibit tumor growth without obvious side effects. 177Lu-MS@PDA holds great potential as a promising radioactive microsphere for HCC.

A clinically translatable kit for MRI/NMI dual-modality nanoprobes based on anchoring group-mediated radiolabeling.

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that 99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[99mTcO4] solution into the kit. In addition, the Fe3O4 nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.

[Effects of age and involved semicircular canals on the caloric test in patients with primary horizontal semicircular canal benign paroxysmal positional vertigo].

Objective:To investigate the effects of age and involved semicircular canals on the results of caloric test in patients with primary horizontal semicircular canal benign paroxysmal positional vertigo（BPPV）. Methods:A total of 258 patients conforming to the diagnosis of primary horizontal semicircular canal BPPV were selected as the case group, and another 110 non-BPPV patients with dizziness/vertigo as the main complaint were selected as the control group. Both groups were divided into elderly group and young and middle-aged group according to their age, and the general information and the results of the caloric test were compared and analyzed for each group. Results: ①There was no statistically significant difference in gender composition and type of involved semicircular canal between the different age groups（P>0.05）；②In patients with horizontal semicircular canal canalolithiasis, there was no statistically significant difference in the rate of abnormal caloric test results between the different age groups（P>0.05）；③In patients with horizontal semicircular canal cupulolithiasis, there was a statistically significant difference in the rate of abnormal caloric test results between the different age groups（P<0.05）；④In the same age group, there was no statistically significant difference in the rate of abnormal caloric test results between the patients with horizontal semicircular canal canalolithiasis and the patients with cupulolithiasis（P>0.05）；⑤In the control group, there was no statistically significant difference between the different age groups in gender composition（P>0.05）；⑥In the control group, there was a statistically significant difference in the rate of abnormal caloric test results between the different age groups（P<0.05）；⑦Among the patients in the same age group, there was no statistically significant difference in the age distribution between the case and control groups（P>0.05）；⑧In patients of the same age group, there was no statistically significant difference in the rate of abnormal caloric test results between the case and control groups（P>0.05）. Conclusion:The involvement of the semicircular canal does not affect the results of the caloric test, but age can affect the results, especially in BPPV patients with horizontal semicircular canal cupulolithiasis.

Functionalized Ultrasmall Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging of Tumor Hypoxia.

Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment's therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitive T1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia via T1-weighted MRI. These promising results may unlock the potential of Fe3O4 nanoparticles as T1-weighted contrast agents for the development of clinical hypoxia probes.

Self-illuminating NIR-II bioluminescence imaging probe based on silver sulfide quantum dots.

Bioluminescence (BL) imaging has emerged to tackle the potential challenges of fluorescence (FL) imaging including the autofluorescence background, inhomogeneous illumination over a wide imaging field, and the light-induced overheating effect. Taking advantage of the bioluminescence resonance energy transfer (BRET) mechanism between a conventional luciferin compound and a suitable acceptor, the visible light of the former can be extended to photons with longer wavelengths emitting from the latter. Although BRET-based self-illuminating imaging probes have already been prepared, employing potentially cytotoxic elements as the acceptor with the emission wavelengths which hardly reach the first near-infrared (NIR-I) window, has limited their applications as safe and high performance in vivo imaging agents. Herein, we report a biocompatible, self-illuminating, and second near-infrared (NIR-II) emissive probe to address the cytotoxicity concerns as well as improve the penetration depth and spatiotemporal resolution of BL imaging. To this end, NanoLuc luciferase enzyme molecules were immobilized on the surface of silver sulfide quantum dots to oxidize its luciferin substrate and initiate a single-step BRET mechanism, resulting in NIR-II photons from the quantum dots. The resulting dual modality (BL/FL) probes were successfully applied to in vivo tumor imaging in mice, demonstrating that NIR-II BL signals could be easily detected from the tumor sites, giving rise to ∼2 times higher signal-to-noise ratios compared to those obtained under FL mode. The results indicated that nontoxic NIR-II emitting nanocrystals deserve more attention to be tailored to fill the growing demands of preparing appropriate agents for high quality BL imaging.