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941.
Veronika Kozlovskaya Yiming Yang Fei Liu Kevin Ingle Aftab Ahmad Ganesh V. Halade Eugenia Kharlampieva 《Molecules (Basel, Switzerland)》2022,27(11)
Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL10-b-PDMS65-b-PVCL10 vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg−1 single dose) of PVCL10-PDMS65-PVCL10 vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research. 相似文献
942.
Kevin B. Wu Christopher J. A. Skrodzki Qiwen Su Jennifer Lin Jia Niu 《Chemical science》2022,13(23):6873
The functions of natural nucleic acids such as DNA and RNA have transcended genetic information carriers and now encompass affinity reagents, molecular catalysts, nanostructures, data storage, and many others. However, the vulnerability of natural nucleic acids to nuclease degradation and the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications. Herein, we report the synthesis and polymerase recognition of a 5-(octa-1,7-diynyl)uracil 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) triphosphate. The DNA-templated, polymerase-mediated primer extension using this “click handle”-modified FANA (cmFANA) triphosphate and other FANA nucleotide triphosphates consisting of canonical nucleobases efficiently generated full-length products. The resulting cmFANA polymers exhibited excellent nuclease resistance and the ability to undergo efficient click conjugation with azide-functionalized molecules, thereby becoming a promising platform for serving as a programmable and evolvable synthetic genetic polymer capable of post-polymerization functionalization.Polymerase-mediated incorporation of a “click handle”-modified fluoroarabinonucleic acid (cmFANA) triphosphate produces a new class of nuclease-resistant, evolvable genetic polymers that can be functionalized with azide-containing molecules. 相似文献
943.
Ronald V. Emmons Tiffany Liden Kevin A. Schug Emanuela Gionfriddo 《Journal of separation science》2020,43(9-10):1915-1924
The continued rise in the extraction of unconventional oil and gas across the globe poses many questions about how to manage these relatively new waste‐streams. Produced water, the primary waste by‐product, contains a diverse number of anthropogenic additives together with the numerous hydrocarbons extracted from the well. Due to potential environmental hazards, it is critical to characterize the chemical composition of this type of waste before proper disposal or remediation/reuse. In this work, a thin film solid phase microextraction approach was developed and optimized to characterize produced water. The thin film device consisted of hydrophilic‐lipophilic balance particles embedded in polydimethylsiloxane and immobilized on a carbon mesh surface. These devices were chosen to provide broad extraction coverage and high reusability. Various parameters were evaluated to ensure reproducible results while minimizing analyte loss. This optimized protocol, consisting of a 15 min extraction followed by a short (3 s) rinsing step, enabled the reproducible analysis of produced water without any sample pretreatment. Extraction efficiency was suitable for both produced water additives and hydrocarbons. The developed approach was able to tentatively identify a total of 201 compounds from produced water samples, by using one‐dimensional gas chromatography hyphenated to mass spectrometry and data deconvolution. 相似文献
944.
Aranit Harizaj Olivier Q. De Clercq Benedicte Descamps Christian Vanhove Stefaan C. De Smedt Dirk Poelman Ine Lentacker Kevin Braeckmans 《Particle & Particle Systems Characterization》2019,36(11)
Dendritic cell (DC)‐based vaccines for immunotherapy have already achieved promising results in the last decade. To further improve current treatment protocols and enhance the therapeutic outcome, noninvasive in vivo tracking of DCs remains of crucial importance. Persistent luminescent nanoparticles (PLNPs) are inorganic materials which show an afterglow for hours after the optical excitation has ceased. If the afterglow is in the near‐infrared, the emission of injected particles can be tracked in vivo. However, stability and toxicity issues limit the use of bare PLNPs for biological applications. Therefore, appropriate surface functionalization is needed to improve their biocompatibility. In this study, it is demonstrated that near‐infrared light emitting LiGa5O8:Cr3+ nanoparticles can be functionalized with a biocompatible lipid coating which provides them with outstanding stability in biological media. In vitro experiments show efficient uptake, absence of cytotoxicity even at very high particle concentrations, and no adverse effects on the maturation potential of DCs. DCs labeled with lipid‐coated LiGa5O8:Cr3+ nanoparticles injected in mice can be imaged over days, confirming efficient in vivo migration to the popliteal lymph node. Together the results show that lipid coated LiGa5O8:Cr3+ nanoparticles possess excellent possibilities for further use in research and development of DC based vaccines. 相似文献
945.
Alessia Petti Matthew C. Leech Anthony D. Garcia Iain C. A. Goodall Adrian P. Dobbs Kevin Lam 《Angewandte Chemie (International ed. in English)》2019,58(45):16115-16118
A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono‐ and multi‐functionalised γ‐butyrolactones were synthesised through exo‐cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp3–sp3 capture of the newly formed carbon‐centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology. This represents a viable synthetic route towards pharmaceutically important fragments and further demonstrates the practicality of electrosynthesis as a green and economical method to activate small organic molecules. 相似文献
946.
Foundations of Chemistry - There are inherent difficulties in a subject like chemistry particularly the notion of a chemical reaction. In this paper the difficulties are discussed from a teaching... 相似文献
947.
Chen‐Ming Lin Maritess Arancillo Jonathan Whisenant Kevin Burgess 《Angewandte Chemie (International ed. in English)》2020,59(24):9398-9402
Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well‐defined patterns. Bioinformatics studies to match side‐chain orientations of a novel hydantoin triazole chemotype ( 1 ) to protein‐protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein‐protein interaction uPA?uPAR. Consequently, chemotype 1 was made with appropriate side‐chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing. 相似文献
948.
We evaluate two competing hypotheses that try to account for robust violations of the predictions of game theory in Ultimatum bargaining experiments. One popular hypothesis is that the subjects are motivated by considerations of fairness that are not modelled by traditional theory. The alternative hypothesis is that the subjects do not have common knowledge of the rationality, beliefs and motives of other players. Each hypothesis can explain existing data. We design several experiments to discriminate between these two hypotheses. The results provide strong support for the alternative hypothesis. 相似文献
949.
950.
The Discrete Wavelet Transform (DWT) is of considerable practical use in image and signal processing applications. For example,
significant compression can be achieved through the use of the DWT. A fundamental problem with the DWT, however, is the treatment
of finite length data sequences. Commonly used techniques such as circular convolution and symmetric extension can produce
undesirable edge effects which propagate into the interior of the transformed data as the number of DWT iterations increases.
In this paper, we develop a DWT applicable to Daubechies’ orthogonal wavelets which does not exhibit edge effects. The underlying
idea is to extrapolate the data at the boundaries by determining the coefficients of a best fit polynomial through data points
in the vicinity of the boundary. This approach can be regarded as a solution to the problem of orthogonal wavelets on an interval.
However, it has the advantage that it does not involve the explicit construction of boundary wavelets. The extrapolated DWT
is designed to be well conditioned and to produce a critically sampled output. The methods we describe are equally applicable
to biorthogonal wavelet bases. 相似文献