Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Targeted co-delivery of doxorubicin and TPGS to breast cancer cells by PLGA coated magnetic nanoparticles
Download
index.pdf
Date
2017
Author
Metin, Esra
Metadata
Show full item record
Item Usage Stats
261
views
69
downloads
Cite This
Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells also effect as cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.The targeting strategy can be changed depending on carrier types, but magnetic nanoparticles are commonly preferred due to their easy targetable features by using external magnetic field. In this study, poly(dl-lactic-co-glycolic acid) (PLGA) coated magnetic nanoparticles were synthesized for targeted co-delivery of doxorubicin and vitamin E TPGS to breast cancer cells. TPGS is known as an inhibitor of multidrug resistance, enhancer of cellular drug uptake and drug release rate. The magnetic nanoparticles were synthesized by coprecipitation method, and then coated with oleic acid. Coated nanoparticles were encapsulated in PLGA and TPGS polymer and drug loaded form of this polymeric magnetic nanoparticle was also produced. vi Synthesized nanoparticles were characterized by using FTIR, zeta-potential, XPS, VSM, DLS, TGA, SEM, TEM and spectrophotometric analyses. The results showed that the nanoparticles were spherical, superparamagnetic and drug loaded nanoparticle (NP) size was 121 nm which is in the range for successful targeting. Moreover, TPGS and doxorubicin loading were confirmed by TGA and FTIR analysis. Drug loading and release profiles were studied. It was found that 177 µg doxorubicin was loaded on 1 mg Dox-PLGA-TPGS-MNP (Dox NPT20) nanoparticle and 155 µg on Dox PLGA-MNP (Dox NPT0). In both types of nanoparticles, a sustained release profile was obtained. Internalization of magnetic polymeric nanoparticles was detected by Prussian blue staining technique. The NPs were taken by cells in 5 hours. Presence of TPGS on core material increased the cellular internalization of nanoparticles in human breast adenocarcinoma cell lines (drug sensitive MCF-7 and doxorubicin resistant MCF-7/Dox cells). Moreover, the targetable properties of magnetic polymeric nanoparticles were shown by applying an external magnetic field. XTT cell proliferation assay indicated that drug free nanoparticles did not killed the cells (MCF-7 and MCF-7/Dox) and the cytotoxic effects of drug loaded nanoparticles on drug sensitive and drug resistant cell lines were shown. The cytotoxic effects of drug loaded nanoparticles increased in the presence of TPGS in core. In addition, TPGS increased the drug accumulation in drug resistant cells. Doxorubicin and TPGS loaded magnetic polymeric nanoparticles due to their size, biocompatibility, cytotoxicity and targetable properties could be used in new generation targeted chemotherapy.
Subject Keywords
Doxorubicin.
,
Drug resistance.
,
Drug delivery systems.
,
Cancer
URI
http://etd.lib.metu.edu.tr/upload/12620788/index.pdf
https://hdl.handle.net/11511/26285
Collections
Graduate School of Natural and Applied Sciences, Thesis
Suggestions
OpenMETU
Core
Co-delivery of Doxorubicin and D-alpha-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles
Metin, Esra; Mutlu, Pelin; Gündüz, Ufuk (2018-01-01)
Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Synthesis and characterization of polyethylene glycol coated magnetic nanoparticles and their use for anti-cancer drug delivery
Erdem, Murat; Gündüz, Ufuk; Azarkan, Serap Yalçın; Department of Biology (2014)
Although conventional chemotherapy is the most valid method to cope with cancer, it has many drawbacks such as decrease in production of blood cells, inflammation of the lining of the digestive tract, hair loss etc. Reasons for its side effects are that drugs used in chemotherapy are distributed evenly within the body of a patient and cannot distinguish the cancer cells from the healthy ones. To decrease the negative effects of chemotherapeutic drugs and to increase their efficiency, many drug delivery syst...
Metastatic behaviour of doxorubicin resistant MCF-7 breast cancer cells after Vimentin silencing
Tezcan, Okan; Gündüz, Ufuk; Department of Biology (2013)
Chemotherapy is one of the common treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). MDR is caused by the activity of diverse ATP binding cassette (ABC) transporters that pump drugs out of the cells. There are several drugs which have been used in treatment of cancer. One of them is doxorubicin that intercalates and inhibits DNA replication. However, doxorubicin has been found to cause development of MDR ...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
E. Metin, “Targeted co-delivery of doxorubicin and TPGS to breast cancer cells by PLGA coated magnetic nanoparticles,” M.S. - Master of Science, Middle East Technical University, 2017.
