Article: article from journal or magazin.
Specific targeting of cancer cells by multifunctional mitoxantrone-conjugated magnetic nanoparticles.
Journal of Drug Targeting
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Cell Line, Tumor, Dopamine/administration & dosage, Dopamine/chemistry, Drug Delivery Systems/methods, Ferric Compounds/administration & dosage, Ferric Compounds/chemistry, Folic Acid Transporters/metabolism, Humans, MCF-7 Cells, Magnetics/methods, Mitoxantrone/administration & dosage, Mitoxantrone/chemistry, Nanoparticles/administration & dosage, Nanoparticles/chemistry, Neoplasms/drug therapy, Neoplasms/metabolism, Particle Size, Polyethylene Glycols/administration & dosage, Polyethylene Glycols/chemistry, Spectroscopy, Fourier Transform Infrared/methods
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