83578-21-6Relevant articles and documents
Ternary-responsive magnetic nanocarriers for targeted delivery of thiol-containing anticancer drugs
Ghorbani, Marjan,Hamishehkar, Hamed,Hajipour, Hamed,Arsalani, Naser,Entezami, Ali Akbar
, p. 3561 - 3570 (2016)
Cancer is currently the second leading cause of death in the world and one of the most serious challenges in medical therapy. Targeted nanocarrier systems potentially propose a solution to the severe side effects associated with direct drug delivery to the tumor cells (conventional chemotherapy). A novel multi (magnetic, thermo, pH and redox) responsive drug nanocarrier was successfully prepared through the grafting of poly(N-isopropylacrylamide-co-maleic anhydride-g-S-S-Py), fully characterized by various techniques and subsequently used for loading and targeted delivery of 6-mercaptopurine (6MP), a thiol containing anticancer drug. The in vitro drug release behavior of 6MP over 24 h was investigated in the presence of GSH (10 mM and 2 μM for simulating intra and extracellular conditions, respectively) under physiologic (37 °C, pH 7.4) and simulated cancerous tissue (40 °C, pH 5.3) conditions. The thermo, pH and redox responsive 6MP release ability of the developed nanocarriers was proved through the in vitro drug release study. The cell cytotoxicity study on the Raji (Burkitt lymphoma) cell line indicated efficient performance of multi-responsive 6MP-loaded nanocarriers. It was concluded that the newly developed multi-responsive nanocarriers have promising potential for targeting of thiol containing anticancer drugs to the tumor tissues.
Biodegradable polysilsesquioxane nanoparticles as efficient contrast agents for magnetic resonance imaging
Vivero-Escoto, Juan L.,Rieter, William J.,Lau, Honam,Huxford-Phillips, Rachel C.,Lin, Wenbin
, p. 3523 - 3531 (2013)
Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions. The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53.8 wt% and 49.3 wt% of Gd-DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd-PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5.9 to 17.8 mMs-1 on a per-Gd basis. Finally, the high sensitivity of the Gd-PSQ particles as T1-weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro. The applicability of polysilsesquioxane (PSQ) nanoparticles with cleavable Gd chelates as T1-weighted MRI contrast agents is evaluated in vitro. The chelates are covalently linked via a redox-responsive disulfide moiety, and the platform is further functionalized to improve biocompatibility and cell uptake. The Gd-PSQ particles show high r 1 relaxivity values and strong enhancement of T1-weighted images of human lung and pancreatic cancer cells in vitro. Copyright
Protein and mRNA Delivery Enabled by Cholesteryl-Based Biodegradable Lipidoid Nanoparticles
Chen, Jinjin,Gao, Peiyang,Glass, Zachary,Jarvis, Rachel,Li, Peixuan,Li, Yamin,Ogurlu, Roza,Xu, Qiaobing,Yang, Yongjie,Yu, Yingjie,Zhu, Kuixin
, p. 14957 - 14964 (2020)
Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).
Thiol- And Disulfide-Containing Vancomycin Derivatives against Bacterial Resistance and Biofilm Formation
Gademann, Karl,Shchelik, Inga S.
supporting information, p. 1898 - 1904 (2021/11/16)
Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. Use of the last-resort antibiotic vancomycin is under threat due to the increasing appearance of vancomycin-resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol- and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin-resistant microbes and Gram-negative bacteria. Moreover, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB-resistant Enterococcus compared to vancomycin. This work establishes a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on the structural optimization of antibiotics with sulfur-containing modifications.
Conjugation of Small Molecules to RNA Using a Reducible Disulfide Linker Attached at the 2′-OH Position through a Carbamate Function
Gauthier, Florian,Malher, Astrid,Vasseur, Jean-Jacques,Dupouy, Christelle,Debart, Fran?oise
supporting information, p. 5636 - 5645 (2019/08/22)
A post-synthesis conjugation method was developed to functionalize oligoribonucleotides with various small molecules of biological interest using a reduction-sensitive disulfide linker connected to 2′OH via a carbamate function. For this, first we prepare
Photo-thermal assistant penetration diagnosis and treatment type nanometer medicine (by machine translation)
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Paragraph 0078-0081, (2019/08/12)
The invention belongs to the technical field of biology, and particularly relates to a diagnosis and treatment drug for assisting in deep penetration of tumors by utilizing a photo-thermal effect. The in-situ released probe, under near-infrared illuminati
BICYCLIC PEPTIDE LIGAND STING CONJUGATES AND USES THEREOF
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Paragraph 00422, (2019/03/05)
The present invention provides compounds, compositions thereof, and methods of using the same.
Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Vu, Chi B.,Bridges, Robert J.,Pena-Rasgado, Cecilia,Lacerda, Antonio E.,Bordwell, Curtis,Sewell, Abby,Nichols, Andrew J.,Chandran, Sachin,Lonkar, Pallavi,Picarella, Dominic,Ting, Amal,Wensley, Allison,Yeager, Maisy,Liu, Feng
, p. 458 - 473 (2017/04/26)
A depressed autophagy has previously been reported in cystic fibrosis patients with the common F508del-CFTR mutation. This report describes the synthesis and preliminary biological characterization of a novel series of autophagy activators involving fatty acid cysteamine conjugates. These molecular entities were synthesized by first covalently linking cysteamine to docosahexaenoic acid. The resulting conjugate 1 synergistically activated autophagy in primary homozygous F508del-CFTR human bronchial epithelial (hBE) cells at submicromolar concentrations. When conjugate 1 was used in combination with the corrector lumacaftor and the potentiator ivacaftor, it showed an additive effect, as measured by the increase in the chloride current in a functional assay. In order to obtain a more stable form for oral dosing, the sulfhydryl group in conjugate 1 was converted into a functionalized disulfide moiety. The resulting conjugate 5 is orally bioavailable in the mouse, rat, and dog and allows a sustained delivery of the biologically active conjugate 1.
NO donor-type of gemcitabine/FTA/furazane conjugate and preparation method and use thereof
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Paragraph 0083; 0088; 0089, (2017/08/26)
The invention discloses a gemcitabine/FTA/furazan conjugate in a NO-donor type, a preparation method and an application. A product in the invention is the novel gemcitabine/FTA/furazan conjugate in the NO-donor type or a pharmaceutically-acceptable salt t
FATTY ACID CYSTEAMINE CONJUGATES OF CFTR MODULATORS AND THEIR USE IN TREATING MEDICAL DISORDERS
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, (2016/06/14)
The invention relates to fatty acid cysteamine conjugates of a CFTR modulator, compositions comprising a fatty acid cysteamine conjugate of a CFTR modulator, and methods for using such conjugates and compositions to treat disease, such as a disease caused
