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Both scandium-44 and yttrium-86 are popular PET isotopes with appropriate half-lives for immuno-positron emission tomography (immuno-PET) imaging. Herein, a new bifunctional H4pypa ligand, H4pypa-phenyl-NCS, is synthesized, conjugated to a monoclonal antibody, TRC105, and labeled with both radionuclides to investigate the long-term in vivo stability of each complex. While the 44Sc-labeled radiotracer exhibited promising pharmacokinetics and stability in 4T1-xenograft mice (n = 3) even upon prolonged interactions with blood serum proteins, the progressive bone uptake of the 86Y-counterpart indicated in vivo demetallation, obviating H4pypa as a suitable chelator for Y3+ ion in vivo. The solution chemistry of [natY(pypa)]− was studied in detail and the complex found to be thermodynamically stable in solution with a pM value 22.0, ≥3 units higher than those of the analogous DOTA- and CHX-A′′-DTPA-complexes; the 86Y-result in vivo was therefore most unexpected. To explore further this in vivo lability, Density Functional Theory (DFT) calculation was performed to predict the geometry of [Y(pypa)]− and the results were compared with those for the analogous Sc- and Lu-complexes; all three adopted the same coordination geometry (i.e. distorted capped square antiprism), but the metal-ligand bonds were much longer in [Y(pypa)]− than in [Lu(pypa)]− and [Sc(pypa)]−, which could indicate that the size of the binding cavity is too small for the Y3+ ion, but suitable for both the Lu3+ and Sc3+ ions. Considered along with results from [86Y][Y(pypa-phenyl-TRC105)], it is noted that when matching chelators with radionuclides, chemical data such as the thermodynamic stability and in vitro inertness, albeit useful and necessary, do not always translate to in vivo inertness, especially with the prolonged blood circulation of the radiotracer bound to a monoclonal antibody. Although H4pypa is a nonadentate chelator, which theoretically matches the coordination number of the Y3+ ion, we show herein that its binding cavity, in fact, favors smaller metal ions such as Sc3+ and Lu3+ and further exploitation of the Sc-pypa combination is desired. [ABSTRACT FROM AUTHOR]

Nanozymes are nanomaterial-based artificial enzymes. By effectively mimicking catalytic sites of natural enzymes or harboring multivalent elements for reactions, nanozyme systems have successfully served as direct surrogates of traditional enzymes for catalysis. With the rapid development and ever-deepening understanding of nanotechnology, nanozymes offer higher catalytic stability, ease of modification and lower manufacturing cost than protein enzymes. Additionally, nanozymes possess inherent nanomaterial properties, providing not only a simple substitute of enzymes but also a multimodal platform interfacing complex biologic environments. Recent extensive research has focused on designing various nanozyme systems that are responsive to one or multiple substrates by tailored means. Catalytic activities of nanozymes can be regulated by pH, H2O2 and glutathione concentrations and levels of oxygenation in different microenvironments. Moreover, nanozymes can be remotely-controlled via different stimuli, including a magnetic field, light, ultrasound, and heat. Collectively, these factors can be adjusted to maximize the diagnostic and therapeutic efficacies of different diseases in biomedical settings. Therefore, by integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, we anticipate that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics. [ABSTRACT FROM AUTHOR]

Radiotherapy is a vitally important strategy for clinical treatment of malignant cancers. Therefore, rational design and development of radiosensitizers that could enhance radiotherapeutic efficacy has attracted tremendous attention. Antiangiogenic therapy could be a potentially effective strategy to regulate tumor growth and metastasis since angiogenesis plays a pivotal role in tumor growth, invasion and metastasis to other organs. Herein, we have rationally designed a smart and effective nanosystem by combining ultrasmall selenium nanoparticles and bevacizumab (Avastin™, Av), for simultaneous radiotherapy and antiangiogenic therapy of cancer. The nanosystem was further coated with red blood cell (RBC) membranes to develop the final construct, RBCs@Se/Av. The RBC membrane coating effectively prolongs the blood circulation time and reduces the elimination of the nanosystem by autoimmune responses. As expected, RBCs@Se/Av, when irradiated with X-rays demonstrated potent anticancer and antiangiogenic responses in vitro and in vivo, as evidenced by the strong inhibition of A375 tumor growth in nude mice, without causing any obvious histological damage to the non-target major organs. Taken together, this study demonstrates an effective strategy for the design of a smart Se-based nanosystem decorated with the RBC membrane for simultaneous cancer radiosensitization and precise antiangiogenesis. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is a highly valuable non-invasive imaging tool owing to its exquisite soft tissue contrast, high spatial resolution, lack of ionizing radiation, and wide clinical applicability. Contrast agents (CAs) can be used to further enhance the sensitivity of MRI to obtain information-rich images. Recently, extensive research efforts have been focused on the design and synthesis of high-performance inorganic nanoparticle-based CAs to improve the quality and specificity of MRI. Herein, the basic rules, including the choice of metal ions, effect of electron motion on water relaxation, and involved mechanisms, of CAs for MRI have been elucidated in detail. In particular, various design principles, including size control, surface modification (e.g. organic ligand, silica shell, and inorganic nanolayers), and shape regulation, to impact relaxation of water molecules have been discussed in detail. Comprehensive understanding of how these factors work can guide the engineering of future inorganic nanoparticles with high relaxivity. Finally, we have summarized the currently available strategies and their mechanism for obtaining high-performance CAs and discussed the challenges and future developments of nanoparticulate CAs for clinical translation in MRI. [ABSTRACT FROM AUTHOR]

A small luciferase protein (Nluc) was conjugated to QDs as a bioluminescence resonance energy transfer (BRET) pair. The conjugate showed 76% BRET efficiency and lymph node mapping was successfully performed. The cRGD peptide was conjugated to QD-Nluc for tumor targeting. The self-illuminating QD-Nluc showed excellent energy transfer in a living system and offered an optimal tumor-to-background ratio (＞85). [ABSTRACT FROM AUTHOR]

Both scandium-44 and yttrium-86 are popular PET isotopes with appropriate half-lives for immuno-positron emission tomography (immuno-PET) imaging. Herein, a new bifunctional H 4 pypa ligand, H 4 pypa-phenyl-NCS, is synthesized, conjugated to a monoclonal antibody, TRC105, and labeled with both radionuclides to investigate the long-term in vivo stability of each complex. While the 44 Sc-labeled radiotracer exhibited promising pharmacokinetics and stability in 4T1-xenograft mice (n = 3) even upon prolonged interactions with blood serum proteins, the progressive bone uptake of the 86 Y-counterpart indicated in vivo demetallation, obviating H 4 pypa as a suitable chelator for Y 3+ ion in vivo. The solution chemistry of [ nat Y(pypa)] - was studied in detail and the complex found to be thermodynamically stable in solution with a pM value 22.0, ≥3 units higher than those of the analogous DOTA- and CHX-A''-DTPA-complexes; the 86 Y-result in vivo was therefore most unexpected. To explore further this in vivo lability, Density Functional Theory (DFT) calculation was performed to predict the geometry of [Y(pypa)] - and the results were compared with those for the analogous Sc- and Lu-complexes; all three adopted the same coordination geometry (i.e. distorted capped square antiprism), but the metal-ligand bonds were much longer in [Y(pypa)] - than in [Lu(pypa)] - and [Sc(pypa)] - , which could indicate that the size of the binding cavity is too small for the Y 3+ ion, but suitable for both the Lu 3+ and Sc 3+ ions. Considered along with results from [ 86 Y][Y(pypa-phenyl-TRC105)], it is noted that when matching chelators with radionuclides, chemical data such as the thermodynamic stability and in vitro inertness, albeit useful and necessary, do not always translate to in vivo inertness, especially with the prolonged blood circulation of the radiotracer bound to a monoclonal antibody. Although H 4 pypa is a nonadentate chelator, which theoretically matches the coordination number of the Y 3+ ion, we show herein that its binding cavity, in fact, favors smaller metal ions such as Sc 3+ and Lu 3+ and further exploitation of the Sc-pypa combination is desired.

A γ-AApeptide-based tracer for positron emission tomography imaging of integrin α(v)β(3) is reported. Despite its shorter sequence and linear nature, this tracer had comparable integrin α(v)β(3) binding affinity to the cyclic arginine-glycine-aspartic acid peptide but significantly higher resistance to enzymatic degradation and better stability.

In-depth understanding of the kinetics of the vapor deposition process is substantial for advancing this capable bottom-up nanostructure synthesis approach into a versatile large-scale nanomanufacturing technology. In this paper, we report a systematic study of the vapor deposition kinetics of ZnO nanomaterials under controlled atmosphere and properly refined deposition conditions. The experiments clearly evidenced the self-catalyzed growth of ZnO NWs via the formation of ZnO nanoflowers. This result illustrated how ZnO morphologies were associated with the discrepancy between oxidation rate and condensation rate of Zn. The capability of switching the NW morphologies and possibly mechanisms was demonstrated by kinetically controlling the deposition system. The high Zn composition during the deposition resulted in strongly luminescent NWs, which can be used for optical imaging applications. This research discovered a fundamental kinetics that governs the mechanisms and morphology selection of nanostructures in a non-catalyst growth system.