Antihepatoma activity of multifunctional polymeric nanoparticles via inhibition of microtubules and tyrosine kinases

Nanomedicine ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 381-396
Author(s):  
Radhika Poojari ◽  
Avishkar V Sawant ◽  
Sudarshan Kini ◽  
Rohit Srivastava ◽  
Dulal Panda

Aim: Synthesis of poly-L-lactic acid nanoparticles comprising of microtubule-inhibitor docetaxel and tyrosine kinase inhibitor sorafenib (PLDS NPs) for hepatoma treatment. Materials & methods: PLDS NPs were prepared by the emulsion solvent evaporation method and the anticancer activity was evaluated in Huh7 hepatoma cells. Results: Real-time imaging of quantum dots incorporating poly-L-lactic acid nanoparticles showed a rapid internalization of the nanoparticles in Huh7 cells. PLDS NPs exerted stronger antiproliferative, apoptotic and antiangiogenic effects than free single drug counterparts. They strongly promoted microtubule bundling, multinucleation and increased mitotic index in Huh7 cells. They also inhibited the expression of pERK1/2, pAKT and cyclin D1. Conclusion: We developed a single-nanoscale platform for dual drug delivery and high-sensitivity quantum dots imaging for hepatoma treatment. [Formula: see text]

Author(s):  
Priyanka Verma ◽  
Ravinder Kumar Wanchoo ◽  
Amrit Pal Toor

Sulphonate-grafted-Titania (SO3H-TiO2) quantum dot catalyzed photochemical process offered an energy-efficient, accelerated, and safe approach to synthesize lactic acid esters at ambient temperature conditions. This low-temperature route is conceived in line...


2017 ◽  
Vol 5 (31) ◽  
pp. 6300-6306 ◽  
Author(s):  
Lin Cao ◽  
Xiangqing Li ◽  
Lixia Qin ◽  
Shi-Zhao Kang ◽  
Guodong Li

A new class of Cyt c detection fluorescence sensor based on graphene quantum dots supported by graphene oxide has been facilely developed. The sensor shows a high sensitivity and selectivity for Cyt c detection, and further exhibits favorable intracellular imaging in A549 cells.


2010 ◽  
Vol 654-656 ◽  
pp. 1130-1133 ◽  
Author(s):  
Christopher J. Summers ◽  
Hisham M. Menkara ◽  
Richard A. Gilstrap ◽  
Mazen Menkara ◽  
Thomas Morris

We report the development of new nanoparticle phosphors and quantum dot structures designed for applications to enhance the color rendering and efficiency of high brightness white LEDs, as well as for bio-sensing applications. The intrinsic problem of self-absorption, high toxicity, and high sensitivity to thermal quenching of conventional quantum dot systems has prevented their adoption to LED devices. Doped Cd-free quantum dots may circumvent these issues due to their distinct Stokes shift and improved stability at high temperature. We report on the modification of Mn-doped ZnSe/ZnS core-shell quantum dots for application to the (blue diode + yellow emitter) white LED system. Band gap tuning for 460 nm excitation, inorganic shell growth and in-situ monitoring for enhanced efficiency, and analysis of thermal stability will are reported.


1996 ◽  
Vol 271 (1) ◽  
pp. C255-C263 ◽  
Author(s):  
P. W. Flatman ◽  
N. C. Adragna ◽  
P. K. Lauf

K-Cl cotransport in sheep erythrocytes can be activated by treatment either with A-23187 and EDTA to reduce concentration of internal ionized Mg [Mg]i) to submicromolar levels, with staurosporine, a potent kinase inhibitor, or with N-ethylmaleimide (NEM). Activation by these maneuvers is prevented and reversed by genistein [inhibition constant (Ki) of 15 microM], which inhibits tyrosine kinases (TK). The related glycosidated compound genistin, which does not inhibit TK, does not inhibit transport, whereas another TK inhibitor, tyrphostin B46, inhibits both basal and stimulated transport (Ki of 28 microM). Cotransport activation by NEM is prevented and reversed by the phosphatase inhibitor, calyculin A, and activation by staurosporine occurs only if cells contain ATP. Increasing [Mg]i inhibits cotransport in the presence of calyculin A whether or not staurosporine is present as well. Our work suggests that genistein inhibits cotransport through a TK and that staurosporine and NEM activate cotransport, probably through inhibition of other kinases, causing stimulation through dephosphorylation of a protein (possibly the transporter itself) be a serine/threonine phosphatase. [Mg]i inhibits cotransport by activating a kinase (concentration for half-maximal activation of 10 microM) that phosphorylates this protein.


2015 ◽  
Vol 494 (1) ◽  
pp. 471-478 ◽  
Author(s):  
Mona M.A. Abdel-Mottaleb ◽  
Arnaud Beduneau ◽  
Yann Pellequer ◽  
Alf Lamprecht

Polymers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 895 ◽  
Author(s):  
György Babos ◽  
Emese Biró ◽  
Mónika Meiczinger ◽  
Tivadar Feczkó

Combinatorial drug delivery is a way of advanced cancer treatment that at present represents a challenge for researchers. Here, we report the efficient entrapment of two clinically used single-agent drugs, doxorubicin and sorafenib, against hepatocellular carcinoma. Biocompatible and biodegradable polymeric nanoparticles provide a promising approach for controlled drug release. In this study, doxorubicin and sorafenib with completely different chemical characteristics were simultaneously entrapped by the same polymeric carrier, namely poly(d,l-lactide-co-glycolide) (PLGA) and polyethylene glycol-poly(d,l-lactide-co-glycolide) (PEG-PLGA), respectively, using the double emulsion solvent evaporation method. The typical mean diameters of the nanopharmaceuticals were 142 and 177 nm, respectively. The PLGA and PEG-PLGA polymers encapsulated doxorubicin with efficiencies of 52% and 69%, respectively, while these values for sorafenib were 55% and 88%, respectively. Sustained drug delivery under biorelevant conditions was found for doxorubicin, while sorafenib was released quickly from the PLGA-doxorubicin-sorafenib and PEG-PLGA-doxorubicin-sorafenib nanotherapeutics.


2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Marek Dziadosz ◽  
Michael Klintschar ◽  
Jörg Teske

AbstractBackground:As imatinib gained a lot of attention in the field of medicine, appropriate methods are needed for drug analysis. LC-MS/MS combined with complex sample preparation and column enrichment is usually the method of choice when high sensitivity is necessary. The application of LC-MSMethods:An LC-MSResults:The conditions applied resulted in a limit of detection/quantification value of 0.14/0.45 ng/mL reached without a sophisticated sample preparation technique or enrichment column application. It could be demonstrated that MSConclusions:The presented analytical strategy is an effective way of protein kinase inhibitor analysis in human serum.


Materials ◽  
2022 ◽  
Vol 15 (2) ◽  
pp. 466
Author(s):  
Kaixin Chang ◽  
Qianjin Zhu ◽  
Liyan Qi ◽  
Mingwei Guo ◽  
Woming Gao ◽  
...  

Nitrogen-doped carbon quantum dots (N-CQDs) were synthesized in a one-step hydrothermal technique utilizing L-lactic acid as that of the source of carbon and ethylenediamine as that of the source of nitrogen, and were characterized using dynamic light scattering, X-ray photoelectron spectroscopy ultraviolet-visible spectrum, Fourier-transformed infrared spectrum, high-resolution transmission electron microscopy, and fluorescence spectrum. The generated N-CQDs have a spherical structure and overall diameters ranging from 1–4 nm, and their surface comprises specific functional groups such as amino, carboxyl, and hydroxyl, resulting in greater water solubility and fluorescence. The quantum yield of N-CQDs (being 46%) is significantly higher than that of the CQDs synthesized from other biomass in literatures. Its fluorescence intensity is dependent on the excitation wavelength, and N-CQDs release blue light at 365 nm under ultraviolet light. The pH values may impact the protonation of N-CQDs surface functional groups and lead to significant fluorescence quenching of N-CQDs. Therefore, the fluorescence intensity of N-CQDs is the highest at pH 7.0, but it decreases with pH as pH values being either more than or less than pH 7.0. The N-CQDs exhibit high sensitivity to Fe3+ ions, for Fe3+ ions would decrease the fluorescence intensity of N-CQDs by 99.6%, and the influence of Fe3+ ions on N-CQDs fluorescence quenching is slightly affected by other metal ions. Moreover, the fluorescence quenching efficiency of Fe3+ ions displays an obvious linear relationship to Fe3+ concentrations in a wide range of concentrations (up to 200 µM) and with a detection limit of 1.89 µM. Therefore, the generated N-CQDs may be utilized as a robust fluorescence sensor for detecting pH and Fe3+ ions.


Author(s):  
П. А. Руденко

Доведено, що ізольовані культури виявили високу чутливість до антибіотиків групи β-лактамів (за винятком L. acidophilus №24, L. plantarum «Victoria» №22, L. rhamnosus №5, L. rhamnosus №20 і L. rhamnosus №26, які показали значну варіабельність чутливості до антибактеріальних препаратів наведеної групи, що свідчить про значний потенціал даних мікроорганізмів). Резистентність до аміноглікозидів, лінкозамидів і фторхінолонів (за винятком гатіфлоксацину, який показав високу ефективність по відношенню до всіх молочнокислих мікроорганізмів). The paper shows that the isolated cultures showed high sensitivity to antibiotics of β-lactams (except for L. acidophilus № 24, L. plantarum «Victoria» № 22, L. rhamnosus № 5, L. rhamnosus № 20 and L. rhamnosus № 26, which were characterized by significant variability of sensitivity to antibiotics of this group, which demonstrates the great potential of these microorganisms), resistance to aminoglycosides, lincosamides, and fluoroquinolones (except for gatifloxacin, which has proved to be highly effective against all microorganisms of lactic acid).


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