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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
Other than the above discussed inorganic nanoparticles, there are several other inorganic nanoparticles, such as particles made from silica and silver that have also been used to deliver siRNAs for a wide range of applications. PEI-complexed mesoporous silica nanoparticles showed successful release of loaded siRNA for nearly 30 days in vitro with efficient knock down of target gene expression in vivo [38]. Similarly, siRNA targeting the expression of multidrug resistance-associated protein 1 (MRP1) was delivered using a similar type of PEI-capped mesoporous silica nanoparticles for treating GBM in vitro and in vivo [39]. Silver nanoparticles conjugated to quercetin and siRNA (AgNP-Qe-siRNA) were used to target the antioxidant drug resistance mechanism and to inhibit drug-resistant Bacillus subtilis for effective gene-silencing-assisted antibacterial effect in vitro and in vivo [40].
Breast Imaging with 99mTc-Tetrofosmin
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Enrico del Vecchio, Luigi Mansi, Pier Francesco Rambaldi, Vincenzo Cuccurullo, Biagio Pecori, Mario Quarantelli, Decio Capobianco, Marco Bresciani
It has been demonstrated in different neoplastic cell culture systems that TF shares with MIBI the property of being a substrate for P-glycoprotein (P-gp), a membrane transporter responsible for the multidrug resistance [22-26]. A similar behavior has also been hypothesized with respect to the multidrug resistance-associated protein (MRP), an alternative transporter discovered by Cole [27]. Ballinger [22,23] studied TF and MIBI uptake in wild-type and doxorubicin-resistant variants of the rat MatB and human MCF-7 breast tumor cell lines. Wolf evaluated TF uptake in comparison with MIBI,T1-201 and 99mTc-furifosmin in human drug-sensitive breast and gastric carcinoma cells and in multidrug-resistant cells of breast, gastric, and pancreatic carcinoma [21,24,26,28].
The Role of Platelet-Activating Factor in Endotoxin-Related Disease
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Taco W. Kuijpers, Tom van der Poll
A convincing mechanistic view explaining these phenomena concerning releasability is not available. The multidrug resistance-associated protein (MRP), a 190 kDa product of an ATP-binding cassette transporter gene, has most recently been suggested to have a role in the release of leukotrienes from cells. The endogenous glutathione conjugate of LTC4 had the highest affinity for this transporter. A series of experiments (e.g., photoaffinity labeling and transfection studies) provided evidence that the MRP gene genuinely encodes an ATP-dependent export pump for conjugates of lipophilic compounds with glutathione and several other anionic residues (15). Whether similar “export pumps” are involved in PAF release remains to be clarified.
Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV)
Published in Expert Review of Anti-infective Therapy, 2022
Sandra Abdul Massih, Ahizechukwu C. Eke
Changes in drug transporter activity play significant roles in drug absorption [53]. The most extensively studied intestinal transporters belong to the ATP binding cassette (ABC) family. These include ABCB1, also known as P-glycoprotein (P-gp), ABCG2, also known as breast cancer resistance protein, and ABCC2, called multidrug resistance-associated protein 2 (MRP2) [53]. Almost all the DAA drugs are substrates of P-gp and/or other transporters whose actions can increase or decrease during pregnancy, with the potential to affect drug absorption and bioavailability. Some of these gastrointestinal and hepatic transmembrane transporters undergo changes that occur during pregnancy that can affect the disposition of HCV drugs. For example, OATP1B1/3 is a primary uptake transporter for Grazoprevir (GZR), and there is an approximately 50% decreased expression of OATP1B during pregnancy (as demonstrated in hepatocytes of pregnant rats) [53]. Therefore, it is plausible that due to the decrease in OATP1B expression in the liver/bile ducts during pregnancy, hepatic absorption of GZR would likely decrease during pregnancy. The effects of these drug transporters on HCV drugs during absorption remain unknown and is currently being studied by the International Transport Consortium (ITC).
Overcoming multidrug resistance through targeting ABC transporters: lessons for drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Mohammad Feyzizadeh, Ashkan Barfar, Zeinab Nouri, Muhammad Sarfraz, Parvin Zakeri-Milani, Hadi Valizadeh
Multidrug resistance-associated protein 1 (MRP1) is a 190-kDa phosphoglycoprotein that in humans is encoded by the ABCC1 gene. Structure studies showed that it consists of three TMDs and two NBDs. They are set as TMD0-TMD1-NBD1-TMD2-NBD2 [18,32]. ABCC1 is expressed in several organs and tissues such as the kidney, intestine, BBB, lung, testis, and peripheral blood mononuclear cells; it was first detected in a mutant lung cancer cell line showing resistance to specific anticancer drugs. It is involved in the cellular export of physiological compounds and transports a variety of xenobiotics [18]. In Alzheimer’s patients, amyloid-β (Aβ) accumulation in the brain is critical; deficiency of ABCC1 could increase cerebral Aβ level [18,33]. In addition, ABCC1 has a role in the MDR of tumor cells because it could transport many anticancer drugs to the extracellular environment. The ABCC1 transporter is particularly prevalent in neuroblastoma, lung, breast, and prostate tumors and could interfere with treatment [34]. ABCC1 substrates are mostly amphipathic. They are frequently organic anions conjugated to glutathione conjugates (e.g. doxorubicin and cyclophosphamide), sulfate conjugates, and others such as folic acid, arsenite, and ritonavir. It is noteworthy that different types of efflux pumps may select their substrate from different cell locations so that P-gp substrates are predominantly hydrophobic and could transport substrates from the lipid bilayer, but MRP1 probably gets them from the cytosol [18].
In vitro assessment of the inhibitory effect of goreisan extract and its ingredients on the P-glycoprotein drug transporter and cytochrome P-450 metabolic enzymes
Published in Xenobiotica, 2022
Mikina Takiyama, Takashi Matsumoto, Noriko Kaifuchi, Yasuharu Mizuhara, Eiji Warabi, Katsuya Ohbuchi, Kazushige Mizoguchi
Since Caco-2 cells express various cell surface transporters that are commonly expressed in intestinal epithelial cells including P-gp, breast cancer-resistant protein (BCRP), and multidrug resistance-associated protein 2 (MRP2), they are useful in preclinical drug development studies to help evaluate the inhibitory effects of test compounds on transporters and to confirm whether a test compound is a substrate or an inhibitor of P-gp (Anderle et al. 1998; Hirohashi et al. 2000; Taipalensuu et al. 2001). In this study, we examined the inhibitory effects of goreisan extract and its ingredients on and their ability to inhibit the functionality of P-gp and CYP isoforms. Caco-2 cells, a human colon cancer cell line, exhibit a high morphological and functional similarity to human intestinal epithelial cells and are therefore widely used in experiments to predict drug absorption in humans (Yee 1997; van Breemen and Li 2005). Digoxin, a typical P-gp substrate, exhibited an efflux ratio of 3.09 in Caco-2 cells, which sufficiently indicated the transporter function. In addition, the transport of digoxin was inhibited by verapamil (50 μmol/L), a typical inhibitor of P-gp, indicating that this experimental setup was a valid system for evaluating P-gp-mediated DDIs.