Specific targeting of cancer cells by multifunctional mitoxantrone-conjugated magnetic nanoparticles

Autor:	George Coukos, Mostafa Heidari Majd, Vala Kafil, Hadi Valizadeh, Yadollah Omidi, Jaleh Barar, Davoud Asgari
Rok vydání:	2013
Předmět:	Dopamine Pharmaceutical Science macromolecular substances Polyethylene glycol Conjugated system Ferric Compounds Polyethylene Glycols Magnetics chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor Neoplasms Spectroscopy Fourier Transform Infrared PEG ratio Humans Organic chemistry Moiety Particle Size Bifunctional Chemistry fungi technology industry and agriculture Drug delivery MCF-7 Cells Nanoparticles Magnetic nanoparticles Mitoxantrone Folic Acid Transporters Nuclear chemistry Superparamagnetism
Zdroj:	Journal of Drug Targeting. 21:328-340
ISSN:	1029-2330 1061-186X
DOI:	10.3109/1061186x.2012.750325
Popis:	We report on the synthesis of bifunctional mitoxantrone (MTX)-grafted magnetic nanoparticles (MNPs) modified by dopamine-polyethylene glycol-folic acid (DPA-PEG-FA) for targeted imaging and therapy of cancer. MNPs (~7-10 nm) were synthesized using the thermal decomposition reaction of Fe(acac)3. Bromoacetyl (BrAc) terminal polyethylene glycol dopamine (DPA-PEG-BrAc) was synthesized and treated with ethylene diamine to form bifunctional PEG moiety containing dopamine at one end and amino group at the other end (i.e. DPA-PEG-NH2). It was then reacted with Fe3O4 nanoparticles (NPs) to form Fe3O4-DPA-PEG-NH2 NPs. The activated folic acid (FA) was chemically coupled to Fe3O4-DPA-PEG-NH2, forming Fe3O4-DPA-PEG-FA. MTX was then conjugated to Fe3O4-DPA-PEG-FA, forming Fe3O4-DPA-PEG-FA-MTX. Physicochemical characteristics of the engineered MNPs were determined. The particle size analysis and electron microscopy showed an average size of ~35 nm for Fe3O4-DPA-PEG-FA-MTX NPs with superparamagnetic behavior. FT-IR spectrophotometry analysis confirmed the conjugation of FA and MTX onto the MNPs. Fluorescence microscopy, cytotoxicity assay and flow cytometry analysis revealed that the engineered Fe3O4-DPA-PEG-FA-MTX NPs were able to specifically bind to and significantly inhibit the folate receptor (FR)-positive MCF-7 cells, but not the FR-negative A549 cells. Based upon these findings, we suggest the Fe3O4-DPA-PEG-FA-MTX NPs as an effective multifunctional-targeted nanomedicine toward simultaneous imaging and therapy of FR-positive cancers.
Databáze:	OpenAIRE
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