Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage

Abstract To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitiv...

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Autores principales: Sumit Siddharth, Anmada Nayak, Deepika Nayak, Birendra Kumar Bindhani, Chanakya Nath Kundu
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:3f8a9563eab54721a3be877b8a0a749f2021-12-02T15:06:21ZChitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage10.1038/s41598-017-02134-z2045-2322https://doaj.org/article/3f8a9563eab54721a3be877b8a0a749f2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02134-zhttps://doaj.org/toc/2045-2322Abstract To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells. These cells were resistance to 500 nM of DOX while parental cells were susceptible at 150 nM. The double coated NP caused more cytotoxicity in cancer and MCF-7-DOX-R cells without affecting the normal cells in comparison to DOX-loaded-PLGA-PVA-NP. These NP enhances the uptake of DOX in MCF-7-DOX-R cells and caused apoptosis by increasing apoptotic nuclei, Bax/Bcl-xL ratio, cleaved product PARP-1, tumor suppressor gene p21, p53, topoisomerase inhibition activity, DNA damage and decreasing the migratory potential of cells. An increased S phase arrest was noted in DOX and DOX- loaded- PLGA-PVA-NP treated cells but reduction of S phase and simultaneous increase of Sub-G1 was observed in double coated-NP. Thus, data revealed that CS-DS- DOX- loaded PLGA-PVA- NP caused DOX-resistance cell death by inducing inhibition of topoisomerase activity followed by DNA damage.Sumit SiddharthAnmada NayakDeepika NayakBirendra Kumar BindhaniChanakya Nath KunduNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sumit Siddharth
Anmada Nayak
Deepika Nayak
Birendra Kumar Bindhani
Chanakya Nath Kundu
Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
description Abstract To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells. These cells were resistance to 500 nM of DOX while parental cells were susceptible at 150 nM. The double coated NP caused more cytotoxicity in cancer and MCF-7-DOX-R cells without affecting the normal cells in comparison to DOX-loaded-PLGA-PVA-NP. These NP enhances the uptake of DOX in MCF-7-DOX-R cells and caused apoptosis by increasing apoptotic nuclei, Bax/Bcl-xL ratio, cleaved product PARP-1, tumor suppressor gene p21, p53, topoisomerase inhibition activity, DNA damage and decreasing the migratory potential of cells. An increased S phase arrest was noted in DOX and DOX- loaded- PLGA-PVA-NP treated cells but reduction of S phase and simultaneous increase of Sub-G1 was observed in double coated-NP. Thus, data revealed that CS-DS- DOX- loaded PLGA-PVA- NP caused DOX-resistance cell death by inducing inhibition of topoisomerase activity followed by DNA damage.
format article
author Sumit Siddharth
Anmada Nayak
Deepika Nayak
Birendra Kumar Bindhani
Chanakya Nath Kundu
author_facet Sumit Siddharth
Anmada Nayak
Deepika Nayak
Birendra Kumar Bindhani
Chanakya Nath Kundu
author_sort Sumit Siddharth
title Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
title_short Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
title_full Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
title_fullStr Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
title_full_unstemmed Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
title_sort chitosan-dextran sulfate coated doxorubicin loaded plga-pva-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of dna damage
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3f8a9563eab54721a3be877b8a0a749f
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AT anmadanayak chitosandextransulfatecoateddoxorubicinloadedplgapvananoparticlescausedapoptosisindoxorubicinresistancebreastcancercellsthroughinductionofdnadamage
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AT chanakyanathkundu chitosandextransulfatecoateddoxorubicinloadedplgapvananoparticlescausedapoptosisindoxorubicinresistancebreastcancercellsthroughinductionofdnadamage
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