Unraveling the dynamics of B7-H3-targeting therapeutic antibodies in cancer through PET imaging and antibody pharmacokinetics.

B7-H3, an immunomodulatory protein overexpressed in many cancers, is associated with tumor aggressiveness and poor prognosis, making it a crucial target for imaging to elucidate its role in cancer progression and guide therapeutic interventions. This study employed PET imaging to investigate the in vivo delivery and pharmacokinetics of two anti-B7-H3 antibodies, Ab-1 and Ab-2, in mouse xenograft models with varying B7-H3 expression levels. The antibodies were radiolabeled with [Zr]Zr and evaluated through PET imaging, biodistribution studies, and in vitro assays to assess binding, tumor uptake, and retention.

Simulation and Measurement of Strain Waveform under Vibration Using Fiber Bragg Gratings.

The work is devoted to the consideration of methods for determining the strain of objects using fiber Bragg gratings under a high-frequency vibration or pulsed mechanical action, which is difficult to perform using widespread methods and devices. The methods are based on numerical processing of the time dependence of the radiation power reflected from the fiber Bragg grating at various wavelengths, which makes it possible to measure strain parameters in a wide range of magnitude and frequencies. The efficiency of the proposed methods is demonstrated by numerical simulation.

A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy.

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy.

Breaking Strong Alkynyl-Phenyl Bonds: Poly(-phenylene ethynylene)s under Mechanical Stress.

Stronger chemical bonds withstand higher mechanical forces; thus, the rupture of single bonds is preferred over the rupture of double or triple bonds or aromatic rings. We investigated bond scission in poly(dialkyl--phenylene ethynylene)s (PPEs), a fully conjugated polymer. In a scale-bridging approach using electron-paramagnetic resonance spectroscopy and gel permeation chromatography of cryomilled samples, in combination with density functional theory calculations and coarse-grained simulations, we conclude that mechanical force cleaves the sp-sp bond of PPEs (bond dissociation energy as high as 600 kJ mol).

Distributable, metabolic PET reporting of tuberculosis.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability.

Don't shake it! Mechanical stress testing of mRNA-lipid nanoparticles.

Shaking stress studies are typically performed during formulation development to test the liability of a drug product towards interfacial stress occurring during transport, especially if a liquid formulation is desired. We evaluated various shaking procedures using a polyA-surrogate solution and verified our findings by eGFP-LNP cell-expression experiments. Shaking on an orbital shaker in vertical and horizontal orientations at increasing speeds from 300 to 600 rpm resulted in decreasing levels of encapsulated nucleic acid content, larger LNP sizes, and decreasing PDI.

Numerical Simulation and Measurement of Deformation Wave Parameters by Sensors of Various Types.

The results of applications of various methods for measuring the parameters of high-speed loading using a strain gauge, a fiber Bragg grating located on a metal measuring rod and an interferometer monitoring the movement of the free boundary of the end of the rod are presented. Numerical simulation confirmed the adequacy of the description of the shock-wave process according to experimental data and showed that, with the thickness of the adhesive layer fixing the fiber Bragg grating and the strain gauge on a dimensional rod up to 100 µm, the deformation parameters of the sensors correspond to the parameters of the stress-strain state of the rod. Experimentally, a good correspondence of the results of measuring the magnitude of the relative deformation at a pulse duration of 10-100 µs using sensors of various types is shown, and an estimate of the limit values of the measured values of the deformation wave parameters is given.

Loading test on the oil tank ground settlement performance monitored by an optical parallel scheme.

A loading test of the ground settlement (GS) performance of the oil tank must be examined before beginning its commercial service. This test requires the sensors to be installed around the oil tank, and the GS is measured while water is being filled in, where the liquid level is read with an ultrasonic radar equipment, etc., to indicate the applied water loads.

Distributable, Metabolic PET Reporting of Tuberculosis.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen () and so do not directly correlate with pathogen viability.

Application of Fiber Bragg Gratings as a Sensor of Pulsed Mechanical Action.

The pulsed elongation of fiber Bragg gratings is considered in order to be used to measure the displacement or deformation rate of objects. Optimal measurement modes were determined, numerical simulation of the output signal was performed during pulsed elongation or compression of the fiber grating, and the main patterns were analyzed. The results of the application of the Bragg gratings for the experimental determination of the deformation rate of materials under pulsed magnetic action are presented.

Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics.

NIR-II fluorescence imaging greatly reduces scattering coefficients for nearly all tissue types at long wavelengths, benefiting deep tissue imaging. However, most of the NIR-II fluorophores suffer from low quantum yields and/or short circulation time that limit the quality of NIR-II imaging. Here, we engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a NIR-II quantum yield of 21.

3-F-fluoropropane-1-thiol and F-PEG-1-thiol: Versatile prosthetic groups for radiolabeling maleimide functionalized peptides.

The efficient radiosynthesis of biomolecules utilizing minute quantities of maleimide substrate is important for availability of novel peptide molecular imaging agents. We evaluated both 3-F-fluoropropane-1-thiol and 2-(2-(2-(2-F-fluoroethoxy)ethoxy)ethoxy)ethane-1-thiol (F-fluoro-PEG thiol) as prosthetic groups for radiolabeling under physiological conditions. The precursor employed a benzoate for protection of the thiol and an arylsulfonate leaving group.

Organosilica-Based Hollow Mesoporous Bilirubin Nanoparticles for Antioxidation-Activated Self-Protection and Tumor-Specific Deoxygenation-Driven Synergistic Therapy.

A major concern about glucose oxidase (GOx)-mediated cancer starvation therapy is its ability to induce serious oxidative damage to normal tissues through the massive production of HO byproducts in the oxygen-involved glucose decomposition reaction, which may be addressed by using a HO scavenger, known as an antioxidation agent. Surprisingly, HO removal accelerates the aerobic glycometabolism of tumors by activating the HO-dependent "redox signaling" pathway of cancer cells. Simultaneous oxygen depletion further aggravates tumor hypoxia to increase the toxicity of a bioreductive prodrug, such as tirapazamine (TPZ), thereby improving the effectiveness of cancer starvation therapy and bioreductive chemotherapy.

Disentangling Spectral Phases of Interfering Autoionizing States from Attosecond Interferometric Measurements.

We have determined spectral phases of Ne autoionizing states from extreme ultraviolet and midinfrared attosecond interferometric measurements and ab initio full-electron time-dependent theoretical calculations in an energy interval where several of these states are coherently populated. The retrieved phases exhibit a complex behavior as a function of photon energy, which is the consequence of the interference between paths involving various resonances. In spite of this complexity, we show that phases for individual resonances can still be obtained from experiment by using an extension of the Fano model of atomic resonances.

Tumor Microenvironment-Activated Ultrasensitive Nanoprobes for Specific Detection of Intratumoral Glutathione by Ratiometric Photoacoustic Imaging.

Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellular functions. Precise quantification of GSH via advanced noninvasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable near-infrared spectroscopy (NIR) absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors.

Improving the Theranostic Potential of Exendin 4 by Reducing the Renal Radioactivity through Brush Border Membrane Enzyme-Mediated Degradation.

As highly expressed in insulinomas, the glucagon-like peptide-1 receptor (GLP-1R) is believed to be an attractive target for diagnosis, localization, and treatment with radiolabeled exendin 4. However, the high and persistent radioactivity accumulation of exendin 4 in the kidneys limits accurate diagnosis and safe, as well as effective, radiotherapy in insulinomas. In this study, we intend to reduce the renal accumulation of radiolabeled exendin 4 through degradation mediated by brush border membrane enzymes.

Probing the interplay between geometric and electronic-structure features via high-harmonic spectroscopy.

We present molecular-frame measurements of the recombination dipole matrix element (RDME) in CO, NO, and carbonyl sulfide (OCS) molecules using high-harmonic spectroscopy. Both the amplitudes and phases of the RDMEs exhibit clear imprints of a two-center interference minimum, which moves in energy with the molecular alignment angle relative to the laser polarization. We find that whereas the angle dependence of this minimum is consistent with the molecular geometry in CO and NO, it behaves very differently in OCS; in particular, the phase shift which accompanies the two-center minimum changes sign for different alignment angles.

An Albumin Sandwich Enhances in Vivo Circulation and Stability of Metabolically Labile Peptides.

The effectiveness of numerous molecular drugs is hampered by their poor pharmacokinetics. Different from previous approaches with limited effectiveness, most recently, emerging high-affinity albumin binding moieties (ABMs) for in vivo hitchhiking of endogenous albumin opens up an avenue to chaperone small molecules for long-acting therapeutics. Although several FDA-approved fatty acids have shown prolonged residence and therapeutic effect, an easily synthesized, water-soluble, and high-efficiency ABM with versatile drug loading ability is urgently needed to improve the therapeutic efficacy of short-lived constructs.

A Logic-Gated Modular Nanovesicle Enables Programmable Drug Release for On-Demand Chemotherapy.

It remains a major challenge to achieve precise on-demand drug release. Here, we developed a modular nanomedicine integrated with logic-gated system enabling programmable drug release for on-demand chemotherapy. We employed two different logical AND gates consisting of four interrelated moieties to construct the nanovesicles, denoted as v-A-CED, containing oxidation-responsive nanovesicles (v), radical generators (A), and Edman linker conjugated prodrugs (CED).

In Situ Dendritic Cell Vaccine for Effective Cancer Immunotherapy.

A cancer vaccine is an important form of immunotherapy. Given their effectiveness for antigen processing and presentation, dendritic cells (DCs) have been exploited in the development of a therapeutic vaccine. Herein, a versatile polymersomal nanoformulation that enables generation of tumor-associated antigens (TAAs) and simultaneously serves as adjuvant for an in situ DC vaccine is reported.

Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery.

molecular imaging in the "transparent" near-infrared II (NIR-II) window has demonstrated impressive benefits in reaching millimeter penetration depths with high specificity and imaging quality. Previous NIR-II molecular imaging generally relied on high hepatic uptake fluorophores with an unclear mechanism and antibody-derived conjugates, suffering from inevitable nonspecific retention in the main organs/skin with a relatively low signal-to-background ratio. It is still challenging to synthesize a NIR-II fluorophore with both high quantum yield and minimal liver-retention feature.

Antidiabetic Effect of Abextide, a Long-Acting Exendin-4 Analogue in Cynomolgus Monkeys.

Abextide, synthesized by conjugating an albumin-binding moiety-truncated Evans blue-to glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4, shows extended drug release and enhanced hypoglycemic effect in diabetic mice. The aim of this study is to evaluate the pharmacodynamics of Abextide in nonhuman primates. Two batches of elderly cynomolgus monkeys with naturally occurring diabetes are used for this study.

Single Low-Dose Injection of Evans Blue Modified PSMA-617 Radioligand Therapy Eliminates Prostate-Specific Membrane Antigen Positive Tumors.

Prostate cancer is the most frequently diagnosed malignant tumor in men worldwide. Prostate-specific membrane antigen (PSMA) is a surface molecule specifically expressed by prostate tumors that has been shown to be a valid target for internal radionuclide therapy in both preclinical and clinical settings. The most common radiotherapeutic agent is the small molecule Lu-PSMA-617, which is under clinical evaluation in multiple countries.