Nanoradiopharmaceuticals: An attractive Concept in oncotherapy.

Radiopharmaceuticals are of significant importance in the fields of tumor imaging and therapy. In recent decades, the increasing role of nanotechnology has led to the attractive concept of nanoradiopharmaceuticals. Consequently, it is imperative to provide a concise summary of the necessary guidelines to facilitate the translation of nanoradiopharmaceuticals. In this work, we have presented the contents of radiolabeling strategies and some applications of nanoradiopharmaceuticals. Such a framework can assist researchers in identifying more pertinent insights or making more informed decisions in the study of nanoradiopharmaceuticals.

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. The removal rate of U(VI) from aqueous solution by Ni-pHOF can achieve over 98% in the presence of coexisting nonoxidizing cations and only decreased by less than 8% after five cycles, exhibiting high selectivity and good reusability. Furthermore, Ni-pHOF can remove 86.74% of U(VI) from real low-level radioactive wastewater after 120 min of illumination, showcasing practical application potential. Density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) spectra indicated that modulating the surface charge microenvironment in Ni-pHOF through porphyrin metallization is conducive to improving the charge separation efficiency, prompting more e- and •O2- to participate in the reduction reaction of U(VI). This work provides new insights into the metallization of porphyrin-based HOFs and paves a new way for the tailoring of porphyrin-based HOFs/COFs by modulating the surface charge microenvironment to achieve efficient recovery of U(VI) from real radioactive wastewater.

Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

Branched-Chain-Induced Host-Guest Assembly in Covalent-Organic Frameworks for Efficient Separation of No-Carrier-Added 177Lu.

No-carrier-added (NCA) 177Lu is one of the most interesting nuclides for endoradiotherapy. With the dramatically rapid development of radiopharmaceutical and nuclear medicine, there is a sharp increase in the radionuclide supply of NCA 177Lu, which has formed a great challenge to current radiochemical separation constituted on classical materials. Hence, it is of vital importance to design and prepare new functional materials able of recovering 177Lu from an irradiated target with excellent efficacy. In this work, we proposed to apply noncovalent interactions to regulate the porous properties of covalent organic frameworks (COFs) by tuning the branched chain, rendering related covalent hosts different encapsulation abilities toward a flexible guest, 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (P507). More interestingly, we found that the noncovalent interaction has a great effect on the host-guest complexes, which can achieve efficient NCA 177Lu separation with high recovery (95.97%). A systematic mechanism combined with experimental and theoretical investigations has confirmed that the noncovalent interactions between COFs and P507 play a preeminent role in adjusting the macroscopic properties of the host-guest complexes. This work not only uncovers that noncovalent interactions can affect the basic properties of covalent organic bonded materials but also provides a strategy for the design and preparation of other new moieties with specific functionalities.

A Proof-of-Concept Study on the Theranostic Potential of 177 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, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 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. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) 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, 111In/225Ac-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 111In-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. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Multimodal Imaging-Guided Strategy for Developing 177Lu-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 in vitro, as well as possible administration modes for in vivo cancer therapy. Then, lutetium-177 (177Lu)-labeled MIL-101(Fe)/PEG-FA was prepared for high-sensitive imaging and targeted radiotherapy of glioma in vivo. It has been demonstrated that the obtained 177Lu-labeled MIL-101(Fe)/PEG-FA can work as a complementary probe to rectify the cancer binding affinity of the prepared nanocarrier given by fluorescence imaging, providing more precise biodistribution information. Besides, 177Lu-labeled MIL-101(Fe)/PEG-FA has excellent antitumor effect, leading to cell proliferation inhibition, upregulation of intracellular reactive oxygen species, tumor growth suppression, and immune response-related protein and cytokine upregulation. This work reveals that optical imaging and nuclear imaging can work complementarily as multimodal imaging in the design and evaluation of anticancer nanomedicine, offering a MIL-101(Fe)/PEG-FA-based pharmaceutical with potential in tumor endoradiotherapy.

Sorption behavior and mechanism of U(VI) on Tamusu clay in the presence of U(VI)-CO3 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)-CO3 solution at pH 7.8 by batch experiments. The results demonstrated that the distribution coefficients (Kd) decreased with the increasing values of pHinitial, [U(VI)]initial, and ionic strength, but increased with the extended time and the rising temperature. The sorption was a pH-dependent, heterogeneous, spontaneous, and endothermic chemical process, which could be better described by Freundlich isothermal model and pseudo-second-order kinetic model. The presence of humic acid (HA) or fulvic acid (FA) significantly inhibited the U(VI) sorption, due to the enhanced electrostatic repulsion between the negatively charged HA/FA adsorbed on the clay surface and the negative U(VI) species, as well as the well dispersed HA/FA aggregates in solution wrapping the U(VI) species. The FTIR and XPS spectra indicated that the HCO3- groups on the surface of Tamusu clay after hydroxylation and the ‒OH groups in HA/FA were involved in the U(VI) sorption. The results reported here provide valuable insights into the further understanding of U(VI) migration in geological media.

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. The experiments showed that UPC-H4a removed 98.18% of U(VI) after illumination for 120 min, with high selectivity, strong ion interference resistance, and good reusability. A real low-level radioactive wastewater was employed to estimate the potential of UPC-H4a for practical application and its removal rate can reach 66.14% in the presence of redox competing metal ions, exhibiting great potential for practical application. The DFT calculations and EPR spectra revealed that a more negative electrostatic potential of DAT-porphyrin and the formed intermolecular hydrogen bonds in UPC-H4a can facilitate the participation of photogenerated electrons in the O2/∙O2- reaction, and the radical of ∙O2- was proved to be the critical participant in U(VI) photoreduction. The discovery of UPC-H4a in this work will help to develop more potential applications of HOFs as photocatalysts in radioactive wastewater treatment.

The recent applications of nanotechnology in the diagnosis and treatment of common cardiovascular diseases.

Almost a third of all fatalities may be attributed to cardiovascular disease (CVD), making it a primary cause of mortalities worldwide. Better diagnostic tools and secure, non-invasive imaging techniques are needed to offer accurate information on CVD progression. Several elements contribute to the success of CVD personalized therapy, and two of the most crucial are accurate diagnosis and early detection. The therapy options available for conditions with a pathogenesis that unfold over decades, such as CVD, are very condition-specific and disease-stage based. Nanotechnology is increasingly being used as a therapeutic tool in the biomedical area, where they are used in various contexts, including diagnostics, biosensing, and drug administration. This review article provides an overview of the most recent applications of nanotechnology in the detection and management of prevalent CVDs.

A Radioluminescent Metal-Organic Framework for Monitoring 225Ac in Vivo.

225Ac is considered as one of the most promising radioisotopes for alpha-therapy because its emitted high-energy α-particles can efficiently damage tumor cells. However, it also represents a significant threat to healthy tissues owing to extremely high radiotoxicity if targeted therapy fails. This calls for a pressing requirement of monitoring the biodistribution of 225Ac in vivo during the treatment of tumors. However, the lack of imageable photons or positrons from therapeutic doses of 225Ac makes this task currently quite challenging. We report here a nanoscale luminescent europium-organic framework (EuMOF) that allows for fast, simple, and efficient labeling of 225Ac in its crystal structure with sufficient 225Ac-retention stability based on similar coordination behaviors between Ac3+ and Eu3+. After labeling, the short distance between 225Ac and Eu3+ in the structure leads to exceedingly efficient energy transduction from225Ac-emitted α-particles to surrounding Eu3+ ions, which emits red luminescence through a scintillation process and produces sufficient photons for clearcut imaging. The in vivo intensity distribution of radioluminescence signal originating from the 225Ac-labeled EuMOF is consistent with the dose of 225Ac dispersed among the various organs determined by the radioanalytical measurement ex vivo, certifying the feasibility of in vivo directly monitoring 225Ac using optical imaging for the first time. In addition, 225Ac-labeled EuMOF displays notable efficiency in treating the tumor. These results provide a general design principle for fabricating 225Ac-labeled radiopharmaceuticals with imaging photons and propose a simple way to in vivo track radionuclides with no imaging photons, including but not limited to 225Ac.

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. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.

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. The results showed that as biomineralization proceeded, amorphous uranium-containing deposits were generated and transformed into crystalline minerals outside cells, increasing the overall concentration of uramphite. This is a cumulative rather than abrupt process. Notably, B. thuringiensis X-27 precipitated uranium outside the cell surface within 0.5 h, while the release of Pi into the extracellular environment and the change of pH to alkalescence further promoted the formation of uramphite. In addition, cell viability determination showed that the U(VI) biomineralization induced by B. thuringiensis X-27 was instrumental in alleviating the toxicity of U(VI) to cells. This work offers insight into the mechanism of U(VI) phosphate biomineralization and is a reference for bioremediation-related studies.

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. has been used to treat the uranium-contaminated water, and more than 98% of uranium in the solution can be removed by the alga, when the initial uranium concentration ranges from 10 to 80 mg/L. Especially, an unusual phenomenon of algae-induced uranium biomineralization has been found in the process of uranium bioremediation and its mineralization mechanism has been explored by multiple approaches. It is worth noticing that the biomineralization of uranium induced by Ankistrodsemus sp. is significantly affected by contact time and pH. Uranium is captured rapidly on the cell surface via complexation with the carboxylate radical, amino and amide groups of the microalgae cells, which provides nucleation sites for the precipitation of insoluble minerals. Uranium stimulates Ankistrodsemus sp. to metabolize potassium ions (K+), which may endow algae with the ability to biomineralize uranium into the rose-like compreignacite (K2[(UO2)6O4(OH)6]•8H2O). As the time increased, the amorphous gradually converted into compreignacite crystals and a large number of crystals would expand over both inside and outside the cells. To the best of our knowledge, this is the first investigated microalgae with a time-dependent uranium biomineralization ability and superior tolerance to uranium. This work validates that Ankistrodsemus sp. is a promising alga for the treatment of uranium-contaminated wastewater.

Recent Advances of Anticancer Studies Based on Nano-Fluorescent Metal-Organic Frameworks.

Nano-fluorescent metal-organic frameworks (NF-MOFs), a kind of newly emerged nano-scaled platform, can provide visual, rapid, and highly sensitive optical imaging of cancer lesions both in vitro and in vivo. Meanwhile, the excellent porosity, structural tunability, and chemical modifiability also enable NF-MOFs to achieve simultaneous loading of targeted molecules and therapeutic agents. These NF-MOFs not only possess excellent targeted imaging ability, but also can guide the carried cargos to perform precise therapy, drawing considerable attention in current framework of anticancer drug design. In this review, we outline the fluorescence types and response mechanisms of NF-MOFs, and highlight their applications in cancer diagnosis and therapy in recent years. Based on this panorama, we also discuss current issues and future trends of NF-MOFs in biomedical fields, attempting to clarify the potential value of fluorescence imaging guided anticancer investigations.

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. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. METHODS: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. RESULTS: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. CONCLUSIONS: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TAT-CDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

Targeted Alpha Therapy of Glioma Using 211At-Labeled Heterodimeric Peptide Targeting Both VEGFR and Integrins.

Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment.

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

The dynamic behavior and mechanism of uranium (VI) biomineralization in Enterobacter sp. X57.

The important role of microbes in the biomineralization and migration behavior of uranium in the field of environmental chemistry has been well emphasized in previous work. However, limited work on mineralization processes of indigenous microorganism has prevented us from a deeper understanding of the process and mechanisms of uranium biomineralization. In this work, the dynamic process and mechanism of uranium biomineralization in Enterobacter sp. X57, a novel uranium-tolerant microorganism separated from uranium contaminated soil, were systematically investigated. Enterobacter sp. X57 can induce intracellular mineralization of U (VI) to Uramphite (NH4UO2PO4·3H2O) under neutral conditions by alkaline phosphatase. In this biomineralization process, soluble U (VI) first bonded with the amino and phosphate groups on the plasma membrane, providing initial nucleation site for the formation of U (VI) biominerals. Then the impairment of cell barrier function and the enhancement of alkaline phosphatase metabolism occurred with the accumulation of uranium in cells, creating a possible pathway for soluble U (VI) to diffuse into the cell and be further mineralized into U (VI)-phosphate minerals. All the results revealed that the intracellular biomineralization of uranium by Enterobacter sp. X57 was a combined result of biosorption, intracellular accumulation and phosphatase metabolism. These findings may contribute to a better understanding of uranium biomineralization behavior and mechanism of microorganisms, as well as possible in-situ bioremediation strategies for uranium by indigenous microorganisms.

PET imaging of VEGFR and integrins in glioma tumor xenografts using 89Zr labelled heterodimeric peptide.

Vascular endothelial growth factor receptor (VEGFR) and integrin αv are over-expressed in angiogenesis of variety malignant tumors with key roles in angiogenesis, and have been proven as valuable targets for cancer imaging and treatment. In this study, a heterodimeric peptide targeting VEGFR and integrin was designed, and radiolabeled with zirconium-89 (89Zr) for PET imaging of glioma. 89Zr-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 ± 2.4%. Targeted binding capability of 89Zr-DFO-heterodimeric peptide towards U87MG cells was investigated in murine glioma xenograft models, which shows that the designed probe has good binding ability to both targeting sites. Biodistribution indicated that kidney metabolism is the main pathway and tumor uptake of 89Zr-DFO-heterodimeric peptide reached the peak of 0.62 ± 0.10% ID/g . U87MG xenograft could be clearly visualized by microPET/CT imaging through 1 to 3 h post-injection of 89Zr-DFO-heterodimeric peptide. Importantly, the tumor radiouptake was significantly reduced after blocking, and the imaging effect of this radioactive compound was more obvious than that of monomeric peptide probes. 89Zr-DFO-heterodimeric peptide has been demonstrated to show potential as a new radiopharmaceutical probe towards glioma, and multi-target probes do have advantages in tumor imaging.