Overcoming doxorubicin resistance in cancer: siRNA-loaded nanoarchitectures for cancer gene therapy

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dc.authoridAli Zarrabi / 0000-0003-0391-1769en_US
dc.authorscopusidAli Zarrabi / 23483174100
dc.authorwosidAli Zarrabi / U-2602-2019
dc.contributor.authorDeldar Abad Paskeh, Mahshid
dc.contributor.authorSaebfar, Hamidreza
dc.contributor.authorMahabady, Mahmood Khaksary
dc.contributor.authorOrouei, Sima
dc.contributor.authorHushmandi, Kiavash
dc.contributor.authorZarrabi, Ali
dc.date.accessioned2022-03-23T05:52:48Z
dc.date.available2022-03-23T05:52:48Z
dc.date.issued2022en_US
dc.departmentİstinye Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümüen_US
dc.description.abstractGene therapy can be used as a cancer therapy by affecting signaling networks participating in the aggressive behavior of tumors. Small interfering RNA (siRNA) is a genetic tool employed for gene silencing. The siRNA molecules have a length of 21-22 nucleotides, and are synthetic, short non-coding RNAs. The siRNA molecule should be loaded into the RISC complex to carry out its function to degrade mRNA and reduce protein expression. By targeting oncogenic pathways, siRNA can also promote chemosensitivity and reduce resistance. Doxorubicin (DOX) is an anthracycline family member capable of triggering cell cycle arrest via binding to topoisomerase II and inhibiting DNA replication. The present review focuses on the design of siRNA for increasing DOX sensitivity and overcoming resistance. Molecular pathways such as STAT3, Notch1, Mcl-1 and Nrf2 can be down-regulated by siRNA to promote DOX sensitivity. Furthermore, siRNA can be used to suppress the activity of P-glycoprotein as a cell membrane transporter of drugs, leading to enhanced accumulation of DOX. The co-delivery of DOX and siRNA both incorporated into nanoparticles can increase the intracellular accumulation in cancer cells, and protect siRNA against degradation by enzymes. Furthermore, the circulation time of DOX is lengthened to boost cytotoxicity against cancer cells. The surface modification of nanocarriers with ligands such as RGD or folate increases their selectivity towards cancer cells. Moreover, smart nanostructures, including pH-, redox- and light-responsive are optimized for siRNA and DOX delivery and tumor treatment.en_US
dc.identifier.citationPaskeh MDA, Saebfar H, Mahabady MK, Orouei S, Hushmandi K, Entezari M, Hashemi M, Aref AR, Hamblin MR, Ang HL, Kumar AP, Zarrabi A, Samarghandian S. Overcoming doxorubicin resistance in cancer: siRNA-loaded nanoarchitectures for cancer gene therapy. Life Sci. 2022 Mar 5:120463.en_US
dc.identifier.doi10.1016/j.lfs.2022.120463en_US
dc.identifier.scopus2-s2.0-85126929920en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.1016/j.lfs.2022.120463
dc.identifier.urihttps://hdl.handle.net/20.500.12713/2570
dc.identifier.wosWOS:000793223900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorZarrabi, Ali
dc.language.isoenen_US
dc.relation.ispartofLife Scien_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCancer Chemotherapyen_US
dc.subjectDoxorubicinen_US
dc.subjectDrug Resistanceen_US
dc.subjectGene Therapyen_US
dc.subjectSmart Nanoparticlesen_US
dc.subjectsiRNAen_US
dc.titleOvercoming doxorubicin resistance in cancer: siRNA-loaded nanoarchitectures for cancer gene therapyen_US
dc.typeReview Articleen_US

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