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Molecules, Vol. 25, Pages 2714: Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers
Debart Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions with the risk of a premature release and degradation of the drugs inside the cells. To address this issue, we propose a covalent approach to co-deliver a siRNA-drug conjugate with a redox-responsive self-immolative linker prone to intracellular glutathione-mediated disulfide cleavage. Herein, we report the use...
Source: Molecules - June 10, 2020 Category: Chemistry Authors: Florian Gauthier Jean-R émi Bertrand Jean-Jacques Vasseur Christelle Dupouy Fran çoise Debart Tags: Article Source Type: research

Multidrug Resistance via Lysosomal P-glycoprotein Cell Biology
Localization of the drug transporter P-glycoprotein (Pgp) to the plasma membrane is thought to be the only contributor of Pgp-mediated multidrug resistance (MDR). However, very little work has focused on the contribution of Pgp expressed in intracellular organelles to drug resistance. This investigation describes an additional mechanism for understanding how lysosomal Pgp contributes to MDR. These studies were performed using Pgp-expressing MDR cells and their non-resistant counterparts. Using confocal microscopy and lysosomal fractionation, we demonstrated that intracellular Pgp was localized to LAMP2-stained lysosomes. I...
Source: Journal of Biological Chemistry - November 1, 2013 Category: Chemistry Authors: Yamagishi, T., Sahni, S., Sharp, D. M., Arvind, A., Jansson, P. J., Richardson, D. R. Tags: Cell Biology Source Type: research

A Nitric Oxide Storage and Transport System That Protects Activated Macrophages from Endogenous Nitric Oxide Cytotoxicity Cell Biology
Nitric oxide (NO) is integral to macrophage cytotoxicity against tumors due to its ability to induce iron release from cancer cells. However, the mechanism for how activated macrophages protect themselves from endogenous NO remains unknown. We previously demonstrated by using tumor cells that glutathione S-transferase P1 (GSTP1) sequesters NO as dinitrosyl-dithiol iron complexes (DNICs) and inhibits NO-mediated iron release from cells via the transporter multidrug resistance protein 1 (MRP1/ABCC1). These prior studies also showed that MRP1 and GSTP1 protect tumor cells against NO cytotoxicity, which parallels their roles i...
Source: Journal of Biological Chemistry - December 29, 2016 Category: Chemistry Authors: Hiu Chuen Lok, Sumit Sahni, Patric J. Jansson, Zaklina Kovacevic, Clare L. Hawkins, Des R. Richardson Tags: Cell Biology Source Type: research

Caged-xanthone from Cratoxylum formosum ssp. pruniflorum inhibits malignant cancer phenotypes in multidrug-resistant human A549 lung cancer cells through down-regulation of NF- κB.
Caged-xanthone from Cratoxylum formosum ssp. pruniflorum inhibits malignant cancer phenotypes in multidrug-resistant human A549 lung cancer cells through down-regulation of NF-κB. Bioorg Med Chem. 2018 Dec 31;: Authors: Kaewpiboon C, Boonnak N, Yawut N, Kaowinn S, Chung YH Abstract Our recent study reported that multidrug-resistant (MDR) human A549 lung cancer cells (A549RT-eto) with the elevated expression of NF-κB showed epithelial-mesenchymal transition (EMT), increasing spheroid formation and elevating the expression levels of stemness-related factors, including Oct4, Nanog, Sox2, Bmi1, and Klf4...
Source: Bioorganic and Medicinal Chemistry - December 31, 2018 Category: Chemistry Authors: Kaewpiboon C, Boonnak N, Yawut N, Kaowinn S, Chung YH Tags: Bioorg Med Chem Source Type: research

DNA-Scaffolded Disulfide Redox Network for Programming Drug Delivery Kinetics
Chemistry. 2021 Mar 28. doi: 10.1002/chem.202100149. Online ahead of print.ABSTRACTDynamic covalent materials in response to specific stimuli enable generation of new structures by reversibly forming/breaking chemical bonds, holding a great potential for application in controlled drug release. However, it remains challenging to utilize dynamic covalent chemistry for programming drug delivery kinetics. Here, in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported by utilizing nucleic acids as scaffold of dynamic disulfide bonds. The constructed DdiSRN in response to redox-stimuli allows ...
Source: Chemistry - March 29, 2021 Category: Chemistry Authors: Wei Ji Xiaodan Li Mingshu Xiao Yueyang Sun Wei Lai Hongbo Zhang Hao Pei Li Li Source Type: research