title: Cancer cell targeting and imaging with biopolymer-based nanodevices.
abstract: We report here the synthesis, in vitro and in vivo investigation of magnetic resonance imaging (MRI) active nanoparticles, which target folate receptor overexpressing tumor cells. Self-assembled nanoparticles with a hydrodynamic size of 50-200 nm were prepared from poly-γ-glutamic acid and chitosan biopolymers with Gd-ions. The nanoparticles are biocompatible, non-toxic and stable for several months in aqueous media. In vitro assays using confocal microscopy, flow cytometry and MR imaging on HeLa human cervix carcinoma tumor cells showed that folic acid targeted nanoparticles were internalized specifically in a folate receptor dependent manner. In vivo study confirmed, that, considerable accumulation of nanosystems was found compared with the control animal represented by the MR images. Relaxometry measurements demonstrated that the nanoparticle-Gd complexes drastically change the signal intensity of the tumor cells. Because of the contrast enhancement, they are attractive candidates as potential contrast agents for a variety of diagnostic applications including early diagnosis of tumors.
authors.affiliation: BBS Nanotechnology, H-4225 Debrecen 16, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Hajdu
authors.forename: Magdolna
authors.initials: M
authors.lastname: Bodnár
authors.forename: György
authors.initials: G
authors.lastname: Trencsényi
authors.forename: Teréz
authors.initials: T
authors.lastname: Márián
authors.forename: György
authors.initials: G
authors.lastname: Vámosi
authors.forename: József
authors.initials: J
authors.lastname: Kollár
authors.forename: János
authors.initials: J
authors.lastname: Borbély
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage / Q000737:chemistry; D005682:Gadolinium / Q000008:administration & dosage; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles; D010316:Particle Size; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D048271:Chitosan; D005492:Folic Acid; D005682:Gadolinium