Reference : Synthesis, characterization and in vivo evaluation of a magnetic cisplatin delivery n...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/10993/32913

Title :	Synthesis, characterization and in vivo evaluation of a magnetic cisplatin delivery nanosystem based on PMAA-graft-PEG copolymers
Language :	English
Author, co-author :	Voulgari, E. [Department of Pharmacy, University of Patras, Patras, Greece]
	Bakandritsos, A. [Department of Materials Science, University of Patras, Patras, Greece, Regional Centre for Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University in Olomouc, 17.listopadu 1192/12, Olomouc, Czech Republic]
	Galtsidis, Sotirios [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
	Zoumpourlis, V. [Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece]
	Burke, B. P. [Department of Chemistry and Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, United Kingdom]
	Clemente, G. S. [Department of Chemistry and Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, United Kingdom]
	Cawthorne, C. [Department of Chemistry and Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, United Kingdom]
	Archibald, S. J. [Department of Chemistry and Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, United Kingdom]
	Tuček, J. [Regional Centre for Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University in Olomouc, 17.listopadu 1192/12, Olomouc, Czech Republic]
	Zbořil, R. [Regional Centre for Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University in Olomouc, 17.listopadu 1192/12, Olomouc, Czech Republic]
	Kantarelou, V. [Institute of Nuclear and Particle Physics, NCSR “Demokritos”, Athens, Greece]
	Karydas, A. G. [Institute of Nuclear and Particle Physics, NCSR “Demokritos”, Athens, Greece]
	Avgoustakis, K. [Department of Pharmacy, University of Patras, Patras, Greece]
Publication date :	2016
Journal title :	Journal of Controlled Release
Publisher :	Elsevier B.V.
Volume :	243
Pages :	342-356
Peer reviewed :	Yes (verified by ORBilu)
ISSN :	01683659
Keywords :	[en] Cancer therapy ; Cisplatin ; Drug delivery ; Magnetic targeting ; Nanocarriers ; Theranostics ; Chemical modification ; Computerized tomography ; Electromagnetic field effects ; Histology ; Magnetic fields ; Magnetic resonance imaging ; Magnetism ; Nanomagnetics ; Nanosystems ; Polyacrylates ; Polyethylene glycols ; Polyethylene oxides ; Positron emission tomography ; Tissue ; Toxicity ; Tumors ; Cis-platin ; Nano-carriers ; Platinum compounds ; Article ; HT 29 cell line ; IC50 ; X ray diffraction
Abstract :	[en] The development of anticancer drug delivery systems which retain or enhance the cytotoxic properties of the drug to tumorous tissues, while reducing toxicity to other organs is of key importance. We investigated different poly(methacrylic acid)-g-poly(ethyleneglycol methacrylate) polymers as in situ coating agents for magnetite nanocrystallites. The obtained magnetic nano-assemblies were in turn thoroughly characterized for their structural, colloidal and physicochemical properties (drug loading capacity/release, magnetic field triggered drug release, cell uptake and localization) in order to select the best performing system. With the focus on in vivo validation of such magnetic drug delivery systems for first time, we selected cisplatin as the drug, since it is a potent anticancer agent which exhibits serious side effects due to lack of selectivity. In addition, cisplatin would offer facile determination of the metal content in the animal tissues for biodistribution studies. Alongside post-mortem Pt determination in the tissues, the biodistribution of the drug nanocarriers was also monitored in real time with PET-CT (positron emission tomography/computed tomography) with and without the presence of magnetic field gradients; using a novel chelator-free method, the nanoparticles were radiolabeled with 68Ga without having to alter their structure with chemical modifications for conjugation of radiochelators. The ability to be radiolabeled in such a straightforward but very robust way, along with their measured high MRI response, renders them attractive for dual imaging, which is an important functionality for translational investigations. Their anticancer properties were evaluated in vitro and in vivo, in a cisplatin resistant HT-29 human colon adenocarcinoma model, with and without the presence of magnetic field gradients. Enhanced anticancer efficacy and reduced toxicity was recorded for the cisplatin-loaded nanocarriers in comparison to the free cisplatin, particularly when a magnetic field gradient was applied at the tumor site. Post mortem and real-time tissue distribution studies did not reveal increased cisplatin concentration in the tumor site, suggesting that the enhanced anticancer efficacy of the cisplatin-loaded nanocarriers is driven by mechanisms other than increased cisplatin accumulation in the tumors. © 2016 Elsevier B.V.
Permalink :	http://hdl.handle.net/10993/32913
DOI :	10.1016/j.jconrel.2016.10.021

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