Imaging Properties Research Articles

Core-Alkynylated Fluorescent Flippers: Altered Ultrafast Photophysics to Track Thick Membranes.

Fluorescent flippers have been introduced as small-molecule probes to image membrane tension in living systems. This study describes the design, synthesis, spectroscopic and imaging properties of flippers that are elongated by one and two alkynes inserted between the push and the pull dithienothiophene domains. The resulting mechanophores combine characteristics of flippers, reporting on physical compression in the ground state, and molecular rotors, reporting on torsional motion in the excited state, to take their photophysics to new level of sophistication. Intensity ratios in broadened excitation bands from differently twisted conformers of core-alkynylated flippers thus report on mechanical compression. Lifetime boosts from ultrafast excited-state planarization and lifetime drops from competitive intersystem crossing into triplet states report on viscosity. In standard lipid bilayer membranes, core-alkynylated flippers are too long for one leaflet and tilt or extend into disordered interleaflet space, which preserves rotor-like torsional disorder and thus weak, blue-shifted fluorescence. Flipper-like planarization occurs only in highly ordered membranes of matching leaflet thickness, where they light up and selectively report on these thick membranes with red-shifted, sharpened excitation maxima, high intensity and long lifetime.

Synthesis of metformin-derived fluorescent quantum dots: uptake, cytotoxicity, and inhibition in human breast cancer cells through autophagy pathway

BackgroundBreast cancer remains a challenge for physicians. Metformin, an antidiabetic drug, show promising anticancer properties against cancers. An emerging quantum dot (QD) material improves therapeutic agents’ anticancer and imaging properties. QD are nano-sized particles with extreme application in nanotechnology captured by cells and accumulated inside cells, suggesting bioimaging and effective anticancer outcomes. In this study, a simple one-pot hydrothermal method was used to synthesize fluorescent metformin-derived carbon dots (M-CDs) and then investigated the cytotoxic effects and imaging features on two human breast cancer cell lines including, MCF-7 and MDA-MB-231 cells.ResultsResults showed that M-CDs profoundly decreased the viability of both cancer cells. IC50 values showed that M-CDs were more cytotoxic than metformin either 24–48 h post-treatment. Cancer cells uptake M-CDs successfully, which causes morphological changes in cells and increased levels of intracellular ROS. The number of Oil Red O-positive cells and the expression of caspase-3 protein were increased in M-CDs treated cells. Authophagic factors including, AMPK, mTOR, and P62 were down-regulated, while p-AMPK, Becline-1, LC3 I, and LC3 II were up-regulated in M-CDs treated cells. Finally, M-CDs caused a decrease in the wound healing rate of cells.ConclusionsFor the first, M-CDs were synthesized by simple one-pot hydrothermal treatment without further purification. M-CDs inhibited both breast cancer cells through modulating autophagy signalling.Graphical

64Cu]Cu-FAP-NOX, a N-oxalyl modified cyclic peptide for FAP PET imaging with a flexible imaging time window.

The aim of the present study was to develop a novel 64Cu-labeled cyclic peptide ([64Cu]Cu-FAP-NOX) that targets fibroblast activation protein (FAP) and may offer advantages in terms of image contrast, imaging time window, and low uptake in normal tissues. The novel cyclic peptide featuring with a N-oxalyl modified tail was constructed and conjugated to NOTA for 64Cu labeling. Biochemical and cellular assays were performed with A549.hFAP cells. The performance of [64Cu]Cu-FAP-NOX was compared to that of two established tracers ([64Cu]Cu-FAPI-04 and [68Ga]Ga-FAP-2286) and three different NOTA-conjugates in HEK-293T.hFAP xenograft mice using micro-PET imaging. Ex vivo biodistribution studies were performed to confirm the FAP specificity and to validate the PET data. Furthermore, a first-in-human study of this novel tracer was conducted on one patient with lung cancer. Compared to [64Cu]Cu-FAPI-04, [64Cu]Cu-FAP-NOX demonstrated faster and higher rates of cellular uptake and internalization in A549.hFAP cells, but lower rates of cellular efflux. All six radiotracers were rapidly taken up by the tumor within the first 4h post-injection. However, [64Cu]Cu-FAP-NOX had more intense tumor accumulation and slower washout from the target. The ratios of the tumor to normal tissue (including kidneys and muscles) increased significantly over time, with [64Cu]Cu-FAP-NOX reaching the highest ratio among all tracers. In the patient, [64Cu]Cu-FAP-NOX PET showed a comparable result to FDG PET in the primary malignant lesion while exhibiting higher uptake in pleural metastases, consistent with elevated FAP expression as confirmed by immunohistochemistry. [64Cu]Cu-FAP-NOX is a promising FAP-targeted tracer with a highly flexible imaging time window, as evidenced by preclinical evaluation encompassing biodistribution and micro-PET studies, along with a successful patient application. Furthermore, [64Cu]Cu-FAP-NOX showed enhanced image contrast and favorable pharmacokinetic properties for FAP PET imaging, warranting translation into large cohort studies.

Biomimetic Gold Nanorods-Manganese Porphyrins with Surface-Enhanced Raman Scattering Effect for Photoacoustic Imaging-Guided Photothermal/Photodynamic Therapy.

Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1O2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1O2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy.

Enhancing higher-order modal response in multifrequency atomic force microscopy with a coupled cantilever system.

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM.

Atomic imaging and optical properties of InAs/In0.5Ga0.5As0.5Sb0.5 type II superlattice

High-quality III–V quantum structures, advanced epitaxial technologies, and characterization methods are essential to drive the development of infrared optoelectronic materials and devices. As an important component of type II superlattices, InAs/InxGa1−xAsySb1−y would play an important role in the field of high-performance infrared detectors due to their excellent luminescence efficiency and high crystal quality. However, their interfacial characteristics and the associated minority carrier lifetime are still difficult to identify. In this paper, an atomic imaging technique was used to identify the arrangement and distribution of elements of the InAs/In0.5Ga0.5As0.5Sb0.5 superlattice. Our results confirm the epitaxy mechanism that the quaternary alloy consists of two kinds of ternary alloy in one monolayer. Moreover, by separating the cation and anion columns in the elementally resolved atomic images of the InAs/In0.5Ga0.5As0.5Sb0.5 superlattice, we demonstrate that the interfacial atomic intermixing is less than one molecular layer thickness. Therefore, benefiting from excellent interface quality, InAs/In0.5Ga0.5As0.5Sb0.5 superlattice exhibited high radiation recombination efficiency in the long-wave infrared band (∼8.5 μm), and longer minority carrier lifetime (∼810 ns at 90 K).

Size–mass relations for simulated low-mass galaxies: mock imaging versus intrinsic properties

ABSTRACT The observationally inferred size versus stellar–mass relationship (SMR) for low-mass galaxies provides an important test for galaxy formation models. However, the relationship relies on assumptions that relate observed luminosity profiles to underlying stellar mass profiles. Here we use the Feedback in Realistic Environments simulations of low-mass galaxies to explore how the predicted SMR changes depending on whether one uses star-particle counts directly or mock observations. We reproduce the SMR found in The Exploration of Local Volume Satellites survey remarkably well only when we infer stellar masses and sizes using mock observations. However, when we use star particles to directly infer stellar masses and half-mass radii, we find that our galaxies are too large and obey an SMR with too little scatter compared to observations. This discrepancy between the ‘true’ galaxy size and mass and those derived in the mock observation approach is twofold. First, our simulated galaxies have higher and more varied mass-to-light ratios (MLR) at a fixed colour than those commonly adopted, which tends to underestimate their stellar masses compared to their true, simulated values. Second, our galaxies have radially increasing MLR gradients therefore using a single MLR tends to underpredict the mass in the outer regions. Similarly, the true half-mass radius is larger than the half-light radius because the light is more concentrated than the mass. If our simulations are accurate representations of the real Universe, then the relationship between galaxy size and stellar mass is even tighter for low-mass galaxies than is commonly inferred from observed relations.

Immunoregulatory Engineering of Semiconducting Charge-Reversal Nanoantioxidant for Ameliorating Cancer Radioimmunotheranostics.

Radiotherapy (RT) is a crucial clinical modality for cancer. However, nonselectivity, toxicity to normal tissues, and radio-resistance severely limit RT applications. This study develops a versatile X-ray theranostic nano-antioxidant (XTN) to prevent normal tissues from oxidative damage and induce systematic and robust anticancer immunity. XTN owns NIR-II photoacoustic (PA) imaging properties for precise discrimination of the tumor margin through, thereby improving the accuracy of RT. Additionally, XTN is a nano-antioxidant to enhance the cell viability of normal cells after irradiation. Most importantly, XTN scavenges reactive oxygen species (ROS) in the TME to preserve the stimulatory activity of released high mobility group protein B1 to dendritic cells (DCs) and recover T cells' immune function. Meanwhile, XTN achieves charge-reversal specifically releasing an immunomodulator (demethylcantharidin, DMC) in the acidic TME. Moreover, the specifically released DMC inhibits protein phosphatase-2A activity and reduces regulatory T cell (Treg) differentiation. In the bilateral 4T1 tumor model, XTN-mediated radioimmunotherapy remarkably boosts a systemic antitumor immune response and induces durable immunological memory against tumor growth.

Self-calibration strategies for reducing systematic slope measurement errors of autocollimators in deflectometric profilometry.

Deflectometric profilometers are used to precisely measure the form of beam shaping optics of synchrotrons and X-ray free-electron lasers. They often utilize autocollimators which measure slope by evaluating the displacement of a reticle image on a detector. Based on our privileged access to the raw image data of an autocollimator, novel strategies to reduce the systematic measurement errors by using a set of overlapping images of the reticle obtained at different positions on the detector are discussed. It is demonstrated that imaging properties such as, for example, geometrical distortions and vignetting, can be extracted from this redundant set of images without recourse to external calibration facilities. This approach is based on the fact that the properties of the reticle itself do not change - all changes in the reticle image are due to the imaging process. Firstly, by combining interpolation and correlation, it is possible to determine the shift of a reticle image relative to a reference image with minimal error propagation. Secondly, the intensity of the reticle image is analysed as a function of its position on the CCD and a vignetting correction is calculated. Thirdly, the size ofthe reticle image is analysed as a function of its position and an imaging distortion correction is derived. It is demonstrated that, for different measurement ranges and aperture diameters of the autocollimator, reductions in the systematic errors of up to a factor of four to five can be achieved without recourse to external measurements.

Arrhythmogenic Cardiomyopathy: Current Updates and Future Challenges.

Arrhythmogenic cardiomyopathy (ACM) epitomises a genetic anomaly hallmarked by a relentless fibro-fatty transmogrification of cardiac myocytes. Initially typified as a right ventricular-centric disease, contemporary observations elucidate a frequent occurrence of biventricular and left-dominant presentations. The diagnostic labyrinth of ACM emerges from its clinical and imaging properties, often indistinguishable from other cardiomyopathies. Precision in diagnosis, however, is paramount and unlocks the potential for early therapeutic interventions and vital cascade screening for at-risk individuals. Adherence to the criteria established by the 2010 task force remains the cornerstone of ACM diagnosis, demanding a multifaceted assessment incorporating electrophysiological, imaging, genetic, and histological data. Reflecting the evolution of our understanding, these criteria have undergone several revisions to encapsulate the expanding spectrum of ACM phenotypes. This review seeks to crystallise the genetic foundation of ACM, delineate its clinical and radiographic manifestations, and offer an analytical perspective on the current diagnostic criteria. By synthesising these elements, we aim to furnish practitioners with a strategic, evidence-based algorithm to accurately diagnose ACM, thereby optimising patient management and mitigating the intricate challenges of this multifaceted disorder.

Lighting Up Nucleolus To Report Mitochondria Damage Using a Mitochondria-to-Nucleolus Migration Probe.

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

Imaging findings in otitis media and resulting secondary lesions in dogs and cats - an image essay.

Over the past 2 decades, the increasing availability of computed tomography (CT) and magnetic resonance imaging (MRI) as well as the growing professional expertise have significantly improved the diagnostics of middle and inner ear diseases in dogs and cats. In answering some of the diagnostic questions, CT and MRT demonstrate equivalent performance. For most questions, however, there are differences in the diagnostic performance due to the physical imaging properties of the 2 modalities.CT is more sensitive in demonstrating involvement of the bulla wall and is more effective for detecting abnormal content within the tympanic bulla. In addition, with CT it is often easier to guide tissue samplings. On the other hand, structural changes of the soft tissues of the skull, head, meninges, brain, and nerves are not or only insufficiently detectable on CT images. MRI is clearly superior here. Therefore, MRI is essential for the characterization of materials inside the bulla cavity and for demonstrating the extent of any central spread of otitis media (OM).In this image essay, CT and MRI features of OM and resulting secondary lesions described in the literature are analyzed and summarized. Own image examples are used for illustration. Information on the etiology, pathogenesis, pathomorphology, and clinical signs important for understanding these changes are presented in concise descriptions.

A Novel Multi-Effect Photosensitizer for Tumor Destruction via Multimodal Imaging Guided Synergistic Cancer Phototherapy.

How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.

27‐2: Nine‐Depth Switchable Augmented Reality Display with Bi‐stacked Quarter‐Waveplate‐Based Geometric Phase Lenses

Here, we present triple sets of wavefront modulation by proposing quarter‐waveplate‐based GPL (QWP GPL). We demonstrate nine depth‐switchable AR imaging functions with a bi‐stack condition of the QWP GPL modules. The presented QWP‐based GPL module scheme is advantageous for increasing depth‐switchable layers without increasing the switchable optic units required. In addition, the AR display optics based on the QWP GPL module can further improve form‐factor issues and AR imaging properties.

Characteristics of Sizing Materials Used in Persian Medieval Manuscripts: Physical, Optical, Spectral Imaging, and Fungicidal Properties

ABSTRACT In this study, we investigated the diverse range of materials used for sizing in Iranian paper manuscripts during the Timurid (fifteenth century) to Safavid (sixteenth century) and Qajar (nineteenth century) periods. Our approach combined historical analysis with scientific examination of reconstructed sizings. We reconstructed 15 sizing materials based on identified Persian historical recipes and analysed their physical, optical, and spectral characteristics. Additionally, we assessed their behaviour against the mould fungus Aspergillus flavus. The results revealed distinctive properties for each sizing material, shedding light on their potential applications in paper preservation. Furthermore, our investigation demonstrated variations in hygroscopicity, thickness, grammage, and ash content post-sizing. The sizing materials also exhibited different effects on paper reflectance properties. Additionally, our study revealed insights into the impact of sizing on burnished papers, indicating that the mechanical process of burnishing did not significantly alter the chemical composition or spectral properties of the paper, with only minor changes in brightness observed in specific cases. All tested sizing materials supported varying levels of mould growth, indicating potential implications for paper conservation. Our findings provide valuable insights into the historical practices of Iranian paper sizing and offer practical considerations for the preservation of paper manuscripts.

A NIR-Fluorochrome for Live Cell Dual Emission and Lifetime Tracking from the First Plasma Membrane Interaction to Subcellular and Extracellular Locales.

Molecular probes with the ability to differentiate between subcellular variations in acidity levels remain important for the investigation of dynamic cellular processes and functions. In this context, a series of cyclic peptide and PEG bio-conjugated dual near-infrared emissive BF2-azadipyrromethene fluorophores with maxima emissions at 720 nm (at pH > 6) and 790 nm (at pH < 5) have been developed and their aqueous solution photophysical properties determined. Their inter-converting emissions and fluorescence lifetime characteristics were exploited to track their spatial and temporal progression from first contact with the plasma membrane to subcellular locales to their release within extracellular vesicles. A pH-dependent reversible phenolate/phenol interconversion on the fluorophore controlled the dynamic changes in dual emission responses and corresponding lifetime changes. Live-cell confocal microscopy experiments in the metastatic breast cancer cell line MDA-MB-231 confirmed the usability of the dual emissive properties for imaging over prolonged periods. All three derivatives performed as probes capable of real-time continuous imaging of fundamental cellular processes such as plasma membrane interaction, tracking endocytosis, lysosomal/large acidic vesicle accumulation, and efflux within extracellular vesicles without perturbing cellular function. Furthermore, fluorescence lifetime imaging microscopy provided valuable insights regarding fluorophore progression through intracellular microenvironments over time. Overall, the unique photophysical properties of these fluorophores show excellent potential for their use as information-rich probes.

Indocyanine green-loaded N-doped carbon quantum dot nanoparticles for effective photodynamic therapy and cell imaging of melanoma cancer: in vitro, ex vivo and in vivo study

Background Indocyanine Green (ICG) as an agent for photodynamic therapy (PDT) of melanoma cancer has low quantum yield, short circulation half-life, poor photo-stability, and tendency to aggregation. Purpose N-doped carbon quantum dot (CQD) nanoparticle was applied to encapsulate ICG and overcome ICG obstacle in PDT with simultaneous cell imaging property. Methods CQD was prepared using hydrothermal method. Cell culture study and In vivo assessments on C57BL/6 mice containing melanoma cancer cells was performed. Results Results showed that CQD size slightly enhanced from 24.55 nm to 42.67 nm after ICG loading. Detection of reactive oxygen species (ROS) demonstrated that CQD improved ICG photo-stability and ROS generation capacity upon laser irradiation. Cell culture study illustrated that ICG@CQD could decrease survival rate of melanoma cancer cells of B16F10 cell line from 48% for pure ICG to 28% for ICG@CQD. Confocal microscopy images approved more cellular uptake and more qualified cell imaging ability of ICG@CQD. In vivo assessments displayed obvious inhibitory effect of tumor growth for ICG@CQD in comparison to free ICG on the C57BL/6 mice. In vivo fluorescence images confirmed that ICG@CQD accumulates remarkably more than free ICG in tumor region. Finally, ICG@CQD was proposed as an innovative nanocarrier for PDT and diagnosis.

Microsphere-assisted multispectral microscopy

Studies of novel nanostructures have highlighted the need for characterization methods at the nanometric level. To address this challenge, an innovative label-free microsphere-assisted multispectral microscope is presented in this paper. This spectral technique is the first, to our knowledge, to take advantage of the imaging properties of the microsphere. The multispectral acquisition is performed through a 145 µm diameter soda-lime glass microsphere to map the reflectance spectra over a surface covered by an 8 µm diameter disk and with an improved lateral resolution of a factor of 1.8. Relevant reflectance characterizations of materials and sub-diffracted features demonstrate the technique. The proposed setup can be implemented and adapted to any optical microscope.

All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair

Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. Statement of significanceBone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.

Biomimetic Dual-Target Theranostic Nanovaccine Enables Magnetic Resonance Imaging and Chemo/Chemodynamic/Immune Therapy of Glioma.

Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.