P-glycoprotein targeted nanoscale drug carriers

Handle URI:
http://hdl.handle.net/10754/564687
Title:
P-glycoprotein targeted nanoscale drug carriers
Authors:
Li, Wengang ( 0000-0002-1838-8360 ) ; Abu Samra, Dina Bashir Kamil ( 0000-0002-0974-5362 ) ; Merzaban, Jasmeen S. ( 0000-0002-7276-2907 ) ; Khashab, Niveen M. ( 0000-0003-2728-0666 )
Abstract:
Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Smart Hybrid Materials (SHMs) lab; Bioscience Program; Physical Sciences and Engineering (PSE) Division; Chemical Science Program; Advanced Membranes and Porous Materials Research Center
Publisher:
American Scientific Publishers
Journal:
Journal of Nanoscience and Nanotechnology
Issue Date:
1-Feb-2013
DOI:
10.1166/jnn.2013.6084
PubMed ID:
23646646
Type:
Article
ISSN:
15334880
Appears in Collections:
Articles; Bioscience Program; Advanced Membranes and Porous Materials Research Center; Physical Sciences and Engineering (PSE) Division; Controlled Release and Delivery Laboratory; Chemical Science Program; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Wengangen
dc.contributor.authorAbu Samra, Dina Bashir Kamilen
dc.contributor.authorMerzaban, Jasmeen S.en
dc.contributor.authorKhashab, Niveen M.en
dc.date.accessioned2015-08-04T07:12:27Zen
dc.date.available2015-08-04T07:12:27Zen
dc.date.issued2013-02-01en
dc.identifier.issn15334880en
dc.identifier.pmid23646646en
dc.identifier.doi10.1166/jnn.2013.6084en
dc.identifier.urihttp://hdl.handle.net/10754/564687en
dc.description.abstractMulti-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.en
dc.publisherAmerican Scientific Publishersen
dc.subjectDrug deliveryen
dc.subjectInhibitoren
dc.subjectP -glycoproteinen
dc.subjectSNPsen
dc.subjectTargetingen
dc.titleP-glycoprotein targeted nanoscale drug carriersen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentSmart Hybrid Materials (SHMs) laben
dc.contributor.departmentBioscience Programen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentChemical Science Programen
dc.contributor.departmentAdvanced Membranes and Porous Materials Research Centeren
dc.identifier.journalJournal of Nanoscience and Nanotechnologyen
kaust.authorLi, Wengangen
kaust.authorMerzaban, Jasmeen S.en
kaust.authorKhashab, Niveen M.en
kaust.authorAbu Samra, Dina Bashir Kamilen

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