Coassembly Nanomedicine Mediated by Intermolecular Interactions Between Methotrexate and Baricitinib for Improved Rheumatoid Arthritis Treatment.

The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs. The MB NVs with the MTX/BTN weight ratio of 2:1, MB NVs (2:1), showed an improved anti-RA effect through the synergy between the anti-inflammatory and antiproliferative responses. This work presents that the intermolecular interactions between drug molecules could mediate the coassembly behavior into nanomedicine as well as the therapy synergy both in vitro and in vivo, which may provide further understanding on the rational design of combination nanomedicine for therapeutic purposes.

A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2 mg kg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10 mg kg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.

A segmentation network for farmland ridge based on encoder-decoder architecture in combined with strip pooling module and ASPP.

In order to effectively support wheat breeding, farmland ridge segmentation can be used to visualize the size and spacing of a wheat field. At the same time, accurate ridge information collecting can deliver useful data support for farmland management. However, in the farming ridge segmentation scenarios based on remote sensing photos, the commonly used semantic segmentation methods tend to overlook the ridge edges and ridge strip features, which impair the segmentation effect. In order to efficiently collect ridge information, this paper proposes a segmentation method based on encoder-decoder of network with strip pooling module and ASPP module. First, in order to extract context information for multi-scale features, ASPP module are integrated in the deepest feature map. Second, the remote dependence of the ridge features is improved in both horizontal and vertical directions by using the strip pooling module. The final segmentation map is generated by fusing the boundary features and semantic features using an encoder and decoder architecture. As a result, the accuracy of the proposed method in the validation set is 98.0% and mIoU is 94.6%. The results of the experiments demonstrate that the method suggested in this paper can precisely segment the ridge information, as well as its value in obtaining data on the distribution of farmland and its potential for practical application.

Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments.

Macrophages play a crucial role in immune activation and provide great value in the prognosis of cancer treatments. Current strategies for prognostic evaluation of macrophages mainly target the specific biomarkers to reveal the number and distribution of macrophages in the tumors, whereas the phenotypic change of M1 and M2 macrophages in situ is less understood. Here, we designed an ultrasmall superparamagnetic iron oxide nanoparticle-based molecular imaging nanoprobe to quantify the repolarization of M2 to M1 macrophages by magnetic resonance imaging (MRI) using the redox-active nitric oxide (NO) as a vivid chemical target. The nanoprobe equipped with O-phenylenediamine groups could react with the intracellular NO molecules during the repolarization of M2 macrophages to the M1 phenotype, leading to electrical attraction and colloidal aggregation of the nanoprobes. Consequently, the prominent changes of the T1 and T2 relaxation in MRI allow for the quantification of the macrophage polarization. In a 4T1 breast cancer model, the MRI nanoprobe was able to reveal macrophage polarization and predict treatment efficiency in both immunotherapy and radiotherapy paradigms. This study presents a noninvasive approach to monitor the phenotypic changes of M2 to M1 macrophages in the tumors, providing insight into the prognostic evaluation of cancer treatments regarding macrophage-mediated immune responses.

Membrane Proteins and Membrane Curvature: Mutual Interactions and a Perspective on Disease Treatments.

The pathogenesis of various diseases often involves an intricate interplay between membrane proteins and membrane curvature. Understanding the underlying mechanisms of this interaction could offer novel perspectives on disease treatment. In this review, we provide an introduction to membrane curvature and its association with membrane proteins. Furthermore, we delve into the impact and potential implications of this interaction in the context of disease treatment. Lastly, we discuss the prospects and challenges associated with harnessing these interactions for effective disease management, aiming to provide fresh insights into therapeutic strategies.

Selective depolymerization of sugarcane bagasse anaerobic digestate to highly stable phenols-rich bio-oil with the iron-doped K-feldspar catalyst.

Sustainable implementation of thermochemical conversion of biomass to targeted products is dependent on innovations in catalyst design and tuning of structure-property relationships. This study details the use of potassium feldspar (K-feldspar) as a support doped with different iron (Fe) concentrations via wet impregnation (WI) method for hydrothermal liquefaction (HTL) of sugarcane bagasse anaerobic digestate. The Fe/K-feldspar supported catalysts were synthesized and characterized using X-ray diffraction, Inductively Coupled Plasma Optical Emission spectroscopy, Brunauer-Emmet-Teller and Scanning Electron Microscopy analytical methods. Amongst all the catalysts, K-feldspar dopped with 10 wt% Fe (WI-10) was more effective, producing 51.2 wt% bio-crude. The catalyst's activity has been related to the balanced proportion of the microcline: sanidine: haematite (2.8:3.3:1) phases of Fe present on the catalyst, the surface area (porosity), and the surface functionality, thus conferring desirable activity properties. In addition, the WI-10 catalyst had a better selectivity towards substituted phenols that can potentially be used for higher-value applications such as the production of Nylons 6 and 66, and bioplastics. The bio-oil produced with WI-10 has also been demonstrated to be highly stable. The catalyst was reusable up to four times maintaining moderate catalytic performance, and a simple regeneration protocol was shown to restore the activity of the catalyst. The resulting solid residue also exhibited promise as a viable material for use in electrodes for Lithium-ion batteries (LiB). Therefore, this research has demonstrated a promising and sustainable resource recovery strategy for valorising wet biomass wastes into streams of useful products for valuable chemical production and energy application.

Fe(II)-Targeted PET/19F MRI Dual-Modal Molecular Imaging Probe for Early Evaluation of Anticancer Drug-Induced Acute Kidney Injury.

Ferroptosis, an iron-dependent regulated cell death, has been emerging as an early mechanism in anticancer drug-induced acute kidney injury (AKI) that may benefit therapeutic intervention. However, the lack of molecular imaging methods for in vivo detection of ferroptosis restricts the early diagnosis of anticancer drug-induced AKI. Herein, we developed a PET/19F MRI dual-modal imaging probe for the monitoring of ferroptosis in AKI by chemically conjugating the Fe(II)-sensitive artemisinin (Art) motif and macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the CF3-modified polyhedral oligomeric silsesquioxane (POSS) clusters, denoted as the PAD probe. The PAD probe could be converted into PA*D in the presence of Fe(II) ions and subsequently be intercepted by biological macromolecules nearby, thereby enhancing the retention effect in ferroptotic cells and tissues. After labeling with 68Ga isotopes, the 68Ga-labeled PAD probe in cisplatin (CDDP)-induced AKI mice displayed a significantly higher renal uptake level than that in normal mice. Moreover, the PAD probe with a precise chemical structure, relatively high 19F content, and single 19F resonance frequency allowed for interference-free and high-performance19F MRI that could detect the onset of CDDP-induced AKI at least 24 h earlier than the typical clinical/preclinical assays. Our study provides a robust dual-modal molecular imaging tool for the early diagnosis and mechanistic investigation of various ferroptosis-related diseases.

Ferroptosis MRI for early detection of anticancer drug-induced acute cardiac/kidney injuries.

Ferroptosis has been realized in anticancer drug-induced acute cardiac/kidney injuries (ACI/AKI); however, molecular imaging approach to detect ferroptosis in ACI/AKI is a challenge. We report an artemisinin-based probe (Art-Gd) for contrast-enhanced magnetic resonance imaging of ferroptosis (feMRI) by exploiting the redox-active Fe(II) as a vivid chemical target. In vivo, the Art-Gd probe showed great feasibility in early diagnosis of anticancer drug-induced ACI/AKI, which was at least 24 and 48 hours earlier than the standard clinical assays for assessing ACI and AKI, respectively. Furthermore, the feMRI was able to provide imaging evidence for the different mechanisms of action of ferroptosis-targeted agents, either by blocking lipid peroxidation or depleting iron ions. This study presents a feMRI strategy with simple chemistry and robust efficacy for early evaluation of anticancer drug-induced ACI/AKI, which may shed light on the theranostics of a variety of ferroptosis-related diseases.

Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics.

T cells play a determining role in the immunomodulation and prognostic evaluation of cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantify the activity of T cells by exploiting their surface redox status as a chemical target. The T-cell-targeting fusogenic liposomes equipped with 2,2,6,6-tetramethylpiperidine (TEMP) groups neutralize reactive oxygen species protecting T cells from oxidation-induced loss of activity. Meanwhile, the production of paramagnetic 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radicals allows magnetic resonance imaging quantification of the T cell activity. In multiple mouse models, the T-cell-targeting fusogenic liposomes led to efficient tumour inhibition and to early prediction of radiotherapy outcomes. This study uses a chemical targeting strategy to measure the in situ activity of T cells for cancer theranostics and may provide further understanding on engineering T cells for cancer treatment.

A deep learning based method for automatic analysis of high-throughput droplet digital PCR images.

Droplet digital PCR (ddPCR) is a technique for absolute quantification of nucleic acid molecules and is widely used in biomedical research and clinical diagnosis. ddPCR partitions the reaction solution containing target molecules into a large number of independent microdroplets for amplification and performs quantitative analysis of target molecules by calculating the proportion of positive droplets by the principle of Poisson distribution. Accurate recognition of positive droplets in ddPCR images is of great importance to guarantee the accuracy of target nucleic acid quantitative analysis. However, hand-designed operators are sensitive to interference and have disadvantages such as low contrast, uneven illumination, low sample copy number, and noise, and their accuracy and robustness still need to be improved. Herein, we developed a deep learning-based high-throughput ddPCR droplet detection framework for robust and accurate ddPCR image analysis, and the experimental results show that our method achieves excellent performance in the recognition of positive droplets (99.71%) within a limited time. By combining the Hough transform and a convolutional neural network (CNN), our novel method can automatically filter out invalid droplets that are difficult to be identified by local or global encoding methods and realize high-precision localization and classification of droplets in ddPCR images under variable exposure, contrast, and uneven illumination conditions without the need for image pre-processing and normalization processes.

Amine-functionalized MOF-derived carbon materials for efficient removal of Congo red dye from aqueous solutions: simulation and adsorption studies.

In this study, a novel polyethyleneimine (PEI) modified MOF-derived carbon adsorbent (PEI@MDC) was proposed, which exhibited significant adsorption capacity for Congo Red (CR) in aqueous solutions. FT-IR and XPS results showed that PEI was successfully grafted onto MDC, increasing the content of amine groups on the surface of MDC. The adsorption process conformed to the Langmuir isotherm adsorption model and pseudo-second-order kinetic equation, indicating that the adsorption of CR on PEI@MDC was covered by a single layer, and the adsorption process was controlled by chemical processes. According to the Langmuir model, the maximum adsorption capacity at 30 °C was 1723.86 mg g-1. Hydrogen bonding and electrostatic interactions between CR and PEI@MDC surface functional groups were the main mechanisms controlling the adsorption process. After five adsorption-desorption cycles, PEI@MDC still showed a high adsorption capacity for CR, indicating that the adsorbent had an excellent regeneration ability.

Synergism of 64Cu-Labeled RGD with Anti-PD-L1 Immunotherapy for the Long-Acting Antitumor Effect.

We put forward a novel targeting-triggering-therapy (TTT) scheme that combines 64Cu-based targeted radionuclide therapy (TRT) with programmed death-ligand 1 (PD-L1)-based immunotherapy for enhancing therapeutic efficacy. The αvß3 integrin-targeted 64Cu-DOTA-EB-cRGDfK (64Cu-DER) was synthesized. Flow cytometry, immunofluorescence staining, and RT-qPCR were performed to verify PD-L1 upregulation after irradiation with 64Cu-DER. Positron emission tomography imaging was performed to investigate the prominent tumor retention property of 64Cu-DER. In the MC38 tumor model, anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner after 64Cu-DER was injected, followed by the testing of changes in tumor microenvironment (TME). PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 64Cu-DER. The combination of 64Cu-DER TRT (925 MBq/kg) and αPD-L1 mAb (10 mg/kg) resulted in significant delay in tumor growth and protected against tumor rechallenge. Blockade of PD-L1 at 4 h after 64Cu-DER TRT (64Cu-DER + αPD-L1 mAb @ 4 h combination group) was able to achieve 100% survival rate, prevent tumor relapse, and evidently prolong the survival of mice. In summary, the combination of 64Cu-DER and αPD-L1 mAb in a time-dependent manner could be a promising approach to improve therapeutic efficacy. Understandably, this strategy has the potential to extend the scope of 64Cu-based TTT and merits translation into clinical practice for the better management of immune checkpoint blockade immunotherapy.

Technical note: Rapid and high-resolution deep learning-based radiopharmaceutical imaging with 3D-CZT Compton camera and sparse projection data.

BACKGROUND: The Compton camera (CC) has great potential in nuclear medicine imaging due to the high detection efficiency and the ability to simultaneously detect multi-energy radioactive sources. However, the finite resolution of the detectors will degrade the images that the real-world CC can obtain. Besides, the CC sometimes can be limited by the detection efficiency, leading to difficulty in using sparse projection data to realize high-resolution reconstruction with short-time measurement, which limits its clinical application for real-time or rapid radiopharmaceutical imaging. PURPOSE: To overcome the difficulty and promote the usage of the CC in radiopharmaceutical imaging, we present a deep learning (DL)-based CC reconstruction method to realize rapid and high-resolution imaging with short-time measurement. METHODS: We developed a DL-based algorithm MCBP-CCnet via Monte Carlo sampling-based back projection and a dedicated convolutional neural network, called CC-Net, to realize the rapid and high-resolution reconstruction with sparse projection data. A CC prototype based on a single three-dimensional position-sensitive CdZnTe (3D-CZT) detector was used to demonstrate the feasibility of our proposed method. The simulations and experiments of radiopharmaceutical imaging used the 3D-CZT CC and [18 F]NaF. A 3D-printing mouse phantom was also further used to evaluate the performance of the proposed method in animal molecular imaging. RESULTS: The simulation and experimental results showed that the proposed method could realize the images reconstruction within 5 s for list-mode projection data and realized a rapid reconstruction within 35 s for experimental radiopharmaceutical imaging based on the 3D-printing mouse phantom, as well as realized the high-resolution imaging with an accuracy of within 0.78 mm in terms of the sparse projection data that only contained hundreds of events. Besides, the deviations between the reconstructed radiative activities and the exact values were less than 1.51%. CONCLUSION: The results demonstrated that the proposed method could realize the rapid and high-resolution CC reconstruction with sparse projection data obtained by the 3D-CZT CC and realize the high-resolution radiopharmaceutical imaging. The study in this paper also demonstrated the potential and feasibility of future applications of a 3D-CZT CC for real-time high-resolution radiopharmaceutical imaging with short-time measurement.

Effective Adsorption of Colorants from Sugarcane Juice by Bagasse-Based Biochar-Hydroxyapatite Composite.

The clarification of sugarcane juice is a crucial stage in the sugar manufacturing process, as it affects evaporator performance, sugar quality and yield. The emergence of environmentally friendly and efficient adsorption technology has resulted in widespread interest in carbon-based materials. However, their low adsorption capacity and reusability make them unsuitable for processing sugarcane juice. Here, we provide a cost-effective and sustainable method to dope hydroxyapatite (HAP) nanoparticles on porous carbon (BBC) derived from sugarcane bagasse (BBC-HAP). The composite shows excellent adsorption capacity for color extract from sugarcane juice of 313.33 mg/g, far more effective than the commercially available carbon-based adsorbents. Isotherm studies show that the adsorption of BBC-HAP composite to the colorants is a monolayer process. The pseudo-first-order (PFO) and pseudo-second-order (PSO) kinetic models demonstrate that the adsorption process is dominated by chemisorption and supplemented by physical adsorption.

Dual-domain sparse-view CT reconstruction with Transformers.

PURPOSE: Computed Tomography (CT) has been widely used in the medical field. Sparse-view CT is an effective and feasible method to reduce the radiation dose. However, the conventional filtered back projection (FBP) algorithm will suffer from severe artifacts in sparse-view CT. Iterative reconstruction algorithms have been adopted to remove artifacts, but they are time-consuming due to repeated projection and back projection and may cause blocky effects. To overcome the difficulty in sparse-view CT, we proposed a dual-domain sparse-view CT algorithm CT Transformer (CTTR) and paid attention to sinogram information. METHODS: CTTR treats sinograms as sentences and enhances reconstructed images with sinogram's characteristics. We qualitatively evaluate the CTTR, an iterative method TVM-POCS, a convolutional neural network based method FBPConvNet in terms of a reduction in artifacts and a preservation of details. Besides, we also quantitatively evaluate these methods in terms of RMSE, PSNR and SSIM. RESULTS: We evaluate our method on the Lung Image Database Consortium image collection with different numbers of projection views and noise levels. Experiment studies show that, compared with other methods, CTTR can reduce more artifacts and preserve more details on various scenarios. Specifically, CTTR improves the FBPConvNet performance of PSNR by 0.76dB with 30 projections. CONCLUSIONS: The performance of our proposed CTTR is better than the method based on CNN in the case of extremely sparse views both on visual results and quantitative evaluation. Our proposed method provides a new idea for the application of Transformers to CT image processing.

A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti-PD-L1 mAb Combination to Enhance the Antitumor Effect.

PURPOSE: Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy. EXPERIMENTAL DESIGN: We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti-PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis. RESULTS: PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from "cold" to "hot," to make low immunoactivity tumors sensitive to ICB therapy. CONCLUSIONS: In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.

Evans blue-modified radiolabeled fibroblast activation protein inhibitor as long-acting cancer therapeutics.

Rationale: Fibroblast activation protein (FAP) targeted molecular imaging radiotracers have shown promising preclinical and clinical results in tumor diagnosis. However, rapid clearance and inadequate tumor retention of these molecules have hindered them for further clinical translation in cancer therapy. In this study, we aimed to develop a series of albumin binder-truncated Evans blue (EB) modified FAP targeted radiotracers, and optimize the pharmacokinetic (PK) characteristics to overcome the existing limitations in order to apply in the radionuclide therapy of cancer. Methods: A series of compounds with the general structure of EB-FAPI-Bn were synthesized based on a FAP inhibitor (FAPI) variant (FAPI-02) and radiolabeled with 177LuCl3. To verify the binding affinity and FAP targeting specificity of these tracers in vitro, U87MG cell uptake and competition assays were performed. Preclinical PK was evaluated in U87MG tumor-bearing mice using SPECT imaging and biodistribution studies. The lead compound EB-FAPI-B1 was selected and cancer therapeutic efficacy of 177Lu-EB-FAPI-B1 was assessed in U87MG tumor-bearing mice. Results:177Lu-EB-FAPI-B1, B2, B3, B4 were stable in PBS (pH 7.4) and saline for at least 24 h. EB-FAPI-B1 showed high binding affinity (IC50 = 16.5 nM) to FAP in vitro, which was comparable with that of FAPI-02 (IC50 = 10.9 nM). SPECT imaging and biodistribution studies of 177Lu-EB-FAPI-B1, B2, B3, B4 have proved their prominently improved tumor accumulation and retention at 96 h post-injection, especially for 177Lu-EB-FAPI-B1, high tumor uptake and low background signal make it the optimal compound. Compared to the saline group, noteworthy tumor growth inhibitions of 177Lu-EB-FAPI-B1 have been observed after administration of different dosages. Conclusion: In this study, several EB modified FAPI-02 related radiopharmaceuticals have been synthesized successfully and evaluated. High binding affinity and FAP targeting specificity were identified in vitro and in vivo. Remarkably enhanced tumor uptake and retention of EB-FAPI-B1 were found over the unmodified FAPI-02. 177Lu-EB-FAPI-B1 showed remarkable tumor growth suppression in U87MG tumor model with negligible side effects, indicating that 177Lu-EB-FAPI-B1 is promising for clinical application and transformation.

A radioiodinated FR-ß-targeted tracer with improved pharmacokinetics through modification with an albumin binder for imaging of macrophages in AS and NAFL.

PURPOSE: The formation of advanced plaques, which is characterized by the uninterrupted aggregation of macrophages with high expression of folate receptor-ß (FR-ß), is observed in several concomitant metabolic syndromes. The objective of this study was to develop a novel FR-ß-targeted single-photon emission computed tomography (SPECT) radiotracer and validate its application to the noninvasive detection of atherosclerosis (AS) plaque and non-alcoholic fatty liver (NAFL). METHODS: Two radioiodinated probes, [131I]IPBF and [131I]IBF, were developed, and cell uptake studies were used to identify their specific targets for activated macrophages. Biodistribution in normal mice was performed to obtain the pharmacokinetic information of the probes. Apolipoprotein E knockout (ApoE-/-) mice with atherosclerotic aortas were induced by a high-fat and high-cholesterol (HFHC) diet. To investigate the affinity of radiotracers to FR-ß, Kd values were determined using in vitro assays. In addition, the assessments of the aorta in the ApoE-/- mice at different stages were performed using in vivo SPECT/CT imaging, and the findings were compared by histology. RESULTS: Both [131I]IPBF and [131I]IBF were synthesized with > 95% radiochemical purity and up to 3 MBq/nmol molar activity. In vitro assay of [131I]IPBF showed a moderate binding affinity to plasma proteins and specific uptake in activated macrophages. The prolonged blood elimination half-life (t1/2z) of [131I]IPBF (8.14 h) was observed in a pharmacokinetic study of normal mice, which was significantly longer than that of [131I]IBF (t1/2z = 2.95 h). As expected, the Kd values of [131I]IPBF and [131I]IBF in the Raw 264.7 cells were 43.94 ± 9.83 nM and 61.69 ± 15.19 nM, respectively. SPECT imaging with [131I]IPBF showed a high uptake in advanced plaques and NAFL. Radioactivity in excised aortas examined by ex vivo autoradiography further confirmed the specific uptake of [131I]IPBF in high-risk AS plaques. CONCLUSIONS: In summary, we reported a proof-of-concept study of an albumin-binding folate derivative for macrophage imaging. The FR-ß-targeted probe, [131I]IPBF, significantly prolongs the plasma elimination half-life and has the potential for the monitoring of AS plaques and concomitant fatty liver.

Coordinating the Mechanisms of Action of Ferroptosis and the Photothermal Effect for Cancer Theranostics.

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron-chelating agent with BSA, thus leading to biocompatible and stable Cro-Fe@BSA nanoparticles (NPs). The Cro-Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature-dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat-induced formation of heat shock proteins and thus the self-protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro-Fe@BSA NPs also enabled safe and reliable cancer theranostics.