Multivalent At-Radiolabeled Fibroblast Activation Protein Inhibitors for Targeted Alpha-Therapy of Glioma.

Multivalent ligand strategy prevails recently in the design of radioligands for small-molecules due to its successes in enhancing the therapeutic efficacy of radiometallic ligands. In this work, At-FAPI-Dimer and At-APBA-FAPI-Dimer, two multivalent At-conjugated fibroblast activation protein inhibitors (FAPIs), were successfully synthesized with the expectation of narrowing the significant gap between extant radioastatinated FAPIs and clinical application. Cellular pharmacokinetic assessments show that the multivalent strategy could improve the cellular internalization and retention of the radioligand but compromise cellular uptake efficiency relative to monovalent FAPI ligand.

Coordination Confinement on the Decay Chains of Typical Medical α-Radionuclides.

The daughter nuclides in the long decay chain have clouded the translation of the corresponding α-radionuclide therapy. To achieve radioactivity confinement is, therefore, pivotal to the development of medical α-radiopharmaceuticals. Here, we proposed coordination confinement on the decay chains of medical α-radionuclides, employing a versatile crown-ether ligand to adaptively chelate with the decay daughters of typical medical α-radionuclides.

Locoregional radionuclide therapy of glioblastoma with [At]At-PDA-FAPI.

Glioblastoma is the most common and aggressive tumor of the central nervous system. Locoregional administration of therapeutic radiopharmaceuticals appears to be a promising modality for recurrent glioblastomas. In this study, fibroblast activation protein alpha (FAPα) targeting molecule fibroblast activation protein inhibitor-04 (FAPI-04) was conjugated to polydopamine (PDA) nanoparticles, and then, α-emitter astatine-211 was labeled onto the nanocomposite to form [At]At-PDA-FAPI.

Preclinical evaluation of [At]At-AuNP-ABDMPL16 for targeted alpha therapy in Melanoma.

Purpose: The aim of this study is to overcome the challenges of poor tumor penetration and systemic toxicity in targeted alpha therapy (TAT) while also evaluating its immunomodulatory effects to enhance antitumor immune responses in melanoma treatment.

Methods: This study developed a At-labeled single-domain antibody agent ([At]At-AuNP-ABDMPL16) targeting PD-L1, a protein overexpressed in melanoma cells. The binding affinity and internalization of [At]At-AuNP-ABDMPL16 were evaluated in vitro using melanoma cell lines.

Multidimensional exploration of Tc(VII) bio-reduction: Kinetics and cellular responses.

Technetium-99 (Tc) is a long-lived radionuclide that poses significant environmental concerns due to its high mobility, which allows it to persist and spread in contaminated ecosystems. Among the various factors influencing its fate, microbial processes have garnered increasing attention. In this study, we assessed the effects of various environmental conditions on the kinetics of Tc(VII) bio-reduction and, for the first time, investigated the cellular responses triggered by Tc(VII) exposure through multi-omics analysis, with Bacillus cereus strain X-68 (B.

Chemical and Biological Investigations of Antiviral Agents Against Plant Viruses Conducted in China in the 21st Century.

Research into the biology of plant viruses, their mechanisms of pathogenicity, and the induction of host resistance has laid a solid foundation for the discovery of antiviral agents and their targets and the development of effective control technologies. Additionally, recent advancements in fields such as chemical biology, cheminformatics, bioinformatics, and synthetic biology have provided valuable methods and tools for the design of antiviral drugs, the synthesis of drug molecules, assessment of their activity, and investigation of their modes of action. Compared with drug development for human viral diseases, the control of plant viral diseases presents greater challenges, including the cost-benefit of agents, simplification of control technologies, and the effectiveness of treatments.

Lu Radiolabeled Polydopamine Decorated with Fibroblast Activation Protein Inhibitor for Locoregional Treatment of Glioma.

Radionuclide therapy is expected to be a powerful tool for glioma treatment. Here, we introduced a novel nuclear nanomedicine based on polydopamine (PDA), incorporating fibroblast activation protein inhibitor (FAPI) and macrocyclic chelator (DOTA) for specific cancer targeting and Lu labeling. The synthesized nanoradiopharmaceutical, Lu-DOTA-PEG-PDA-FAPI, exhibits good stability in serum, saline and PBS over 5 days.

Strong Affinity between Astatine and Silver: An Available Approach to Anchoring At in Nanocarrier for Locoregional Oncotherapy.

Recently, At-related endoradiotherapy has emerged as an important oncotherapy strategy. Conjugating At with a nanocarrier provides a vital candidate for radionuclide therapy of various malignant tumors. In this study, we proposed utilizing the intrinsically high affinity of heavy halogens and sulfhydryl compounds for metallic silver to achieve highly efficient conjugation between At and Ag-based nanoparticles in a simple way.

At radiolabeled APBA-FAPI for enhanced targeted-alpha therapy of glioma.

Fibroblast activation protein-α (FAPα) is highly expressed in tumor-associated cells and has become one of the most attractive targeting sites in cancer diagnosis and therapy. To ameliorate the rapid metabolism of FAPα inhibitor (FAPI), here, a multifunctional binding agent was introduced to simultaneously achieve At radiolabeling and tumor retention prolongation of corresponding radiolabeled drug. At-APBA-FAPI was successfully synthesized by conjugating At with the designed FAPI carrier in satisfactory radiochemical yield (>60 %).

U(VI) sorption on illite in the Co-existence of carbonates and humic substances.

The presence of carbonates or humic substances (HS) will significantly affect the species and chemical behavior of U(VI) in solution, but lacking systematic exploration of the coupling effect of carbonates and HS under near real environmental conditions at present. Herein, the sorption behavior of U(VI) on illite was systematically studied in the co-existence of carbonates and HS including both humic acid (HA) and fulvic acid (FA) by batch technique. The distribution coefficients (K) increased as function of time and temperature but decreased with increasing concentrations of initial U(VI), Ca, and Mg, as well as ion strength.

Enhanced Photocatalytic Removal of U(VI) from Real Radioactive Wastewater by Modulating the Surface Charge Microenvironment in Porphyrin-Based Hydrogen-Bonded Organic Framework.

Reduction of soluble U(VI) to insoluble U(IV) based on photocatalysts is a simple, environmentally friendly, and efficient method for treating radioactive wastewater. The present study involved the systematic comparison of the photoelectric properties of three metalloporphyrins with different metal centers and the synthesis of a novel porphyrin-based hydrogen-bonded organic framework (Ni-pHOF) photocatalyst by modulating the surface charge microenvironment in porphyrin for enhanced photocatalytic removal of U(VI) from wastewater. Compared to the metal-free HOF, the surface charge microenvironment around the Ni atom in Ni-pHOF accelerated the reduction kinetics of U(VI) under visible light illumination at the initial moment, showing a high removal rate, even in air.

Preparation of Medical Th-Ra Radionuclide Generator Based on SiO@TiO Microspheres.

Ra ( = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current Ra-related therapy is still scarce because of the lack of reliable radionuclide supply.

A Proof-of-Concept Study on the Theranostic Potential of Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation ( Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound.

Biocompatible conjugated polymer nanoparticles labeled with Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, In/Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis.

The biochemical behavior and mechanism of uranium(Ⅵ) bioreduction induced by natural Bacillus thuringiensis.

For a broader understanding of uranium migration affected by microorganisms in natural anaerobic environment, the bioreduction of uranium(Ⅵ) (U(Ⅵ)) was revealed in Bacillus thuringiensis, a dominant bacterium strain with potential of uranium-tolerant isolated from uranium contaminated soil. The reduction behavior was systematically investigated by the quantitative analysis of U(Ⅳ) in bacteria, and mechanism was inferred from the pathway of electron transmission. Under anaerobic conditions, appropriate biomass and sodium lactate as electron donor, reduction behavior of U(Ⅵ) induced by B.

Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice.

Multimodal Imaging-Guided Strategy for Developing Lu-Labeled Metal-Organic Framework Nanomedicine with Potential in Cancer Therapy.

Nano-metal-organic frameworks (nano-MOFs) labeled with radionuclides have shown great potential in the anticancer field. In this work, we proposed to combine fluorescence imaging (FI) with nuclear imaging to systematically evaluate the tumor inhibition of new nanomedicines from living cancer cells to the whole body, guiding the design and application of a high-performance anticancer radiopharmaceutical to glioma. An Fe-based nano-MOF vector, MIL-101(Fe)/PEG-FA, was decorated with fluorescent sulfo-cyanine7 (Cy7) to investigate the binding affinity of the targeting nanocarriers toward glioma cells , as well as possible administration modes for cancer therapy.

Sorption behavior and mechanism of U(VI) on Tamusu clay in the presence of U(VI)-CO complexes.

The sorption behavior of U(VI) on Tamusu clay sampled from a pre-selected high-level radioactive waste (HLW) disposal site in Inner Mongolia (China) was studied systematically in the U(VI)-CO solution at pH 7.8 by batch experiments. The results demonstrated that the distribution coefficients (K) decreased with the increasing values of pH, [U(VI)], and ionic strength, but increased with the extended time and the rising temperature.

Porphyrin-based hydrogen-bonded organic framework for visible light driven photocatalytic removal of U(VI) from real low-level radioactive wastewater.

The reduction of soluble U(VI) to insoluble U(IV) precipitates by visible light is an environmentally friendly and highly effective strategy to remove uranium from uranium-containing radioactive wastewater. Herein, a porous hydrogen-bonded organic framework (HOF) of UPC-H4a was self-assembled by intermolecular hydrogen bonds of 5,10,15,20-tetra(4-(2,4-diaminotriazine)phenyl) porphyrin to remove U(VI) from aqueous solution. UPC-H4a has high crystallinity with permanent porosity, excellent photocatalytic property, good chemical stability, and strong photocatalytic reducibility.

A Smart Benzothiazole-Based Conjugated Polymer Nanoplatform with Multistimuli Response for Enhanced Synergistic Chemo-Photothermal Cancer Therapy.

The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation.

Extracellular biomineralization of uranium and its toxicity alleviation to Bacillus thuringiensis X-27.

Uranium biomineralization can slow uranium migration in the environment and thus prevent it from further contaminating the surroundings. Investigations into the uranium species, pH, inorganic phosphate (Pi) concentration, and microbial viability during biomineralization by microorganisms are crucial for understanding the mineralization mechanism. In this study, Bacillus thuringiensis X-27 was isolated from soil contaminated with uranium and was used to investigate the formation process of uranium biominerals induced by X-27.

Unusual uranium biomineralization induced by green algae: Behavior investigation and mechanism probe.

As a biosorbent, algae are frequently used for the biotreatment or bioremediation of water contaminated by heavy metal or radionuclides. However, it is unclear that whether or not the biomineralization of these metal or radionuclides can be induced by algae in the process of bioremediation and what the mechanism is. In this work, Ankistrodsemus sp.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression.

Background: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT.