title: Dendritic multishell architectures for drug and dye transport.
abstract: Here we present the efficiency and versatility of newly developed core-multishell nanoparticles (CMS NPs), to encapsulate and transport the antitumor drugs doxorubicin hydrochloride (Dox), methotrexate (Mtx) and sodium ibandronate (Ibn) as well as dye molecules, i.e., a tetrasulfonated indotricarbocyanine (ITCC) and nile red. Structurally, the CMS NPs are composed of hyperbranched poly(ethylene imine) core functionalized by alkyl diacids connected to monomethyl poly(ethylene glycol). In order to evaluate their transport in aqueous media in vitro, we have used and compared SEC, UV, ITC, and NMR techniques. We observed that the CMS NPs were able to spontaneously encapsulate and transport Dox, Mtx and nile red in both organic and aqueous media as determined by SEC and UV-VIS spectroscopy. For the VIS transparent Ibn Isothermal Titration Calorimetric (ITC) experiments show an exothermic interaction with the CMS NPs. The enthalpic stabilization (DeltaH) upon encapsulation was in the order of approximately 7 kcals/mol which indicates stable interaction between Ibn and nanoparticles. A T(1) inversion recovery NMR experiment was carried out for 31P and 1H nuclei of Ibn and an increment of spin-lattice relaxation time for respective nuclei was observed upon encapsulation. CMS NPs were also found to encapsulate ITCC dye with stoichiometry of 6-8 molecules/nanocarrier. For in vivo imaging studies the dye loaded CMS NPs were injected to F9 teratocarcinoma bearing mice and a strong contrast was observed in the tumor tissues compared to free dye after 6 h of administration.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Mohiuddin A
authors.initials: MA
authors.lastname: Quadir
authors.forename: Michał R
authors.initials: MR
authors.lastname: Radowski
authors.forename: Felix
authors.initials: F
authors.lastname: Kratz
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Peter
authors.initials: P
authors.lastname: Hauff
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D002151:Calorimetry; D002232:Carbocyanines / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D004396:Coloring Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D004164:Diphosphonates / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008727:Methotrexate / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D010078:Oxazines / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods; D018243:Teratocarcinoma / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002232:Carbocyanines; D004396:Coloring Agents; D004164:Diphosphonates; D004337:Drug Carriers; D010078:Oxazines; C501744:indotricarbocyanine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine; C044808:nile red; D000077557:Ibandronic Acid; D008727:Methotrexate