title: Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy.
abstract: Multifunctional nanoparticles combining therapy and imaging have the potential to improve cancer treatment by allowing personalized therapy. Herein, we aimed to compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of αvβ3 integrin via RGD grafting, (3) magnetic targeting via a magnet placed on the tumor and (4) the combination of magnetic targeting and active targeting of αvβ3 integrin. For a translational approach, PLGA-based nanoparticles loaded with paclitaxel and superparamagnetic iron oxides were used. Electron Spin Resonance spectroscopy and Magnetic Resonance Imaging (MRI) were used to both quantify and visualize the accumulation of multifunctional nanoparticles into the tumors. We demonstrate that compared to untargeted or single targeted nanoparticles, the combination of both active strategy and magnetic targeting drastically enhanced (i) nanoparticle accumulation into the tumor tissue with an 8-fold increase compared to passive targeting (1.12% and 0.135% of the injected dose, respectively), (ii) contrast in MRI (imaging purpose) and (iii) anti-cancer efficacy with a median survival time of 22 days compared to 13 for the passive targeting (therapeutic purpose). Double targeting of nanoparticles to tumors by different mechanisms could be a promising translational approach for the management of therapeutic treatment and personalized therapy.
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schleich
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Po
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, B1 73.12, 1200 Brussels, Belgium; Université Catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Jacobs
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, B1 73.12, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry*; D019344:Lactic Acid; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005290:Ferric Compounds; C000499:ferric oxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel
keywords: MRI; Nanoparticle; Paclitaxel; SPIO; Theranostic; Tumor targeting