Diolein Based Nanostructures as Targeted Theranostics.
Diolein based non-targeted theranostic nanoparticles (DO-NPs) containing 10%wt of the amphiphilic Gadolinium complex (C18)2DTPA(Gd), and targeted NPs, obtained by introducing growing amounts (3% wt, 6% wt or 10% wt) of (C18)2-Peg3000- FA in the sample composition, have been studied for their in vitro and in vivo properties. Cellular binding was studied by lCP-MS analysis of the Gadolinium content and by Surface Plasmon Resonance (SPR) assays. The best formulation in terms of selectivity towards IGROV-1 cells with respect to non-targeted DO-NPs, was that containing 3% (C18)2Peg3000- FA (P < 0.01). Cytotoxic studies and confocal microscopy analysis of IGROV-1 cells indicate high selective properties of the targeted doxorubicin (DOX) loaded NPs. Nanoparticles described here represent the first example in which a targeted carrier characterized by a stable foamy mesophase, provided by the Diolein component, combine the therapeutic effect due to the anticancer drug doxorubicin, with the imaging properties provided by paramagnetic gadolinium complexes for MRI. As evidenced by T(1w), and T(2w) MRI images and by the in vivo antitumor effect in IGROV-1 tumor-bearing mice, DO-NP3-FA/DOX provides very high therapeutic efficacy with a tumor growth regression of 80% and 50% higher as compared to the mice treated with saline solution and with Doxil, respectively.
Antonella
A
Accardo
Francesca
F
Arena
Eliana
E
Gianolio
Daniela
D
Marasco
Paola
P
Ringhieri
Cinzia
C
Boffa
Paola
P
Bardini
Silvia
S
Aime
Giancarlo
G
Morelli
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004075:Diglycerides / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005492:Folic Acid / Q000737:chemistry; D005682:Gadolinium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000737:chemistry*; D013194:Staining and Labeling; D020349:Surface Plasmon Resonance; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004075:Diglycerides; D004317:Doxorubicin; D005492:Folic Acid; D005682:Gadolinium; C013965:diolein