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Polyethylenimine-based Magnetic Nanocomplexes Enhanced Cisplatin Toxicity on Ovarian Cancer Cells in Presence of Static Magnetic Field
Parviz Abdolmaleki
Tarbiat Modares University Faculty of Biological Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4131-2919
License:
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Background
The drug resistance of cancer cells is a major problem in the chemotherapy. Cisplatin (CIS) is one of the most effective chemotherapeutics used for ovarian cancer. Resistance to different chemo-drugs has developed over times. Here, we investigated the experimental approach to increase the CIS cytotoxicity and overcoming cell resistance through nanoparticle-based combination treatments. Polyethylenimine (PEI)-based magnetic iron oxide nanocomplexes were used to transfer the drugs in both genetically matched CIS-resistant (A2780CP) and -sensitive (A2780) ovarian cancer cells in presence of 20 mT static magnetic field. Magnetic nanoparticles (MNPs) were synthesized and bonded to PEI cationic polymer that leads to formation of binary complexes (PM). In the following, binding of CIS to PM binary complexes two including ternary complexes PM/C (PEI-MNP/CIS) and PMC (PEI-MNP-CIS) formed.
Results
Our results showed that the CIS cytotoxicity increased at different concentrations of CIS and PEI in all of binary and ternary treatments overtimes. Furthermore, CIS induced S and G2/M phase’s cell cycle arrest as well as reactive oxygen species (ROS) production in the both cell lines. Ternary complexes enhanced apoptosis more than binary complexes in the treated-cells.
Conclusions
PEI-based magnetic noncomplex can be considered as a novel carrier for increasing the CIS cytotoxicity and probably overcoming drug resistance in ovarian cancer cells.
Keywords
Magnetic iron oxide nanoparticles, Cisplatin, Polyethylenimine, Cytotoxicity, Cell responses
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On 28 Dec, 2020
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This preprint is under consideration at Journal of Ovarian Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Polyethylenimine-based Magnetic Nanocomplexes Enhanced Cisplatin Toxicity on Ovarian Cancer Cells in Presence of Static Magnetic Field
Parviz Abdolmaleki
Tarbiat Modares University Faculty of Biological Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4131-2919
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 05 Jan, 2021
No community comments so far
Reviewers invited
Invitations sent on 18 Jan, 2021
Editor assigned
On 28 Dec, 2020
Submission checks complete
On 28 Dec, 2020
Editor invited
On 28 Dec, 2020
First submitted
On 27 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
The drug resistance of cancer cells is a major problem in the chemotherapy. Cisplatin (CIS) is one of the most effective chemotherapeutics used for ovarian cancer. Resistance to different chemo-drugs has developed over times. Here, we investigated the experimental approach to increase the CIS cytotoxicity and overcoming cell resistance through nanoparticle-based combination treatments. Polyethylenimine (PEI)-based magnetic iron oxide nanocomplexes were used to transfer the drugs in both genetically matched CIS-resistant (A2780CP) and -sensitive (A2780) ovarian cancer cells in presence of 20 mT static magnetic field. Magnetic nanoparticles (MNPs) were synthesized and bonded to PEI cationic polymer that leads to formation of binary complexes (PM). In the following, binding of CIS to PM binary complexes two including ternary complexes PM/C (PEI-MNP/CIS) and PMC (PEI-MNP-CIS) formed.
Results
Our results showed that the CIS cytotoxicity increased at different concentrations of CIS and PEI in all of binary and ternary treatments overtimes. Furthermore, CIS induced S and G2/M phase’s cell cycle arrest as well as reactive oxygen species (ROS) production in the both cell lines. Ternary complexes enhanced apoptosis more than binary complexes in the treated-cells.
Conclusions
PEI-based magnetic noncomplex can be considered as a novel carrier for increasing the CIS cytotoxicity and probably overcoming drug resistance in ovarian cancer cells.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Due to technical limitations, tables are only available as a download in the Supplemental Files section.