title: Passive and electro-assisted delivery of hydrogel nanoparticles in solid tumors, visualized by optical and magnetic resonance imaging in vivo.
abstract: The present study describes a development of nanohydrogel, loaded with QD(705) and manganese (QD(705)@Nanogel and QD(705)@Mn@Nanogel), and its passive and electro-assisted delivery in solid tumors, visualized by fluorescence imaging and magnetic resonance imaging (MRI) on colon cancer-grafted mice as a model. QD(705)@Nanogel was delivered passively predominantly into the tumor, which was visualized in vivo and ex vivo using fluorescent imaging. The fluorescence intensity increased gradually within 30 min after injection, reached a plateau between 30 min and 2 h, and decreased gradually to the baseline within 24 h. The fluorescence intensity in the tumor area was about 2.5 times higher than the background fluorescence. A very weak fluorescent signal was detected in the liver area, but not in the areas of the kidneys or bladder. This result was in contrast with our previous study, indicating that FITC@Mn@Nanogel did not enter into the tumor and was detected rapidly in the kidney and bladder after i.v. injection [J. Mater. Chem. B 2013, 1, 4932-4938]. We found that the embedding of a hard material (as QD) in nanohydrogel changes the physical properties of the soft material (decreases the size and negative charge and changes the shape) and alters its pharmacodynamics. Electroporation facilitated the delivery of the nanohydrogel in the tumor tissue, visualized by fluorescent imaging and MRI. Strong signal intensity was recorded in the tumor area shortly after the combined treatment (QD@Mn@Nanogel + electroporation), and it was observed even 48 h after the electroporation. The data demonstrate more effective penetration of the nanoparticles in the tumor due to the increased permeability of blood vessels at the electroporated area. There was no rupture of blood vessels after electroporation, and there were no artifacts in the images due to a bleeding.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. bakalova@nirs.go.jp.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Bakalova
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia, 1113, Bulgaria.
authors.forename: Biliana
authors.initials: B
authors.lastname: Nikolova
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia, 1113, Bulgaria.
authors.forename: Severina
authors.initials: S
authors.lastname: Atanasova
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia, 1113, Bulgaria.|Medical Faculty, Trakia University, 11 Armejska Str., Stara Zagora, 6000, Bulgaria.
authors.forename: Zhivko
authors.initials: Z
authors.lastname: Zhelev
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Graduate School of Pharmaceutical Sciences and GPLII Program, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kato
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia, 1113, Bulgaria.
authors.forename: Iana
authors.initials: I
authors.lastname: Tsoneva
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: Biomaterials; Clinical/biomedical analysis; Nanoparticles/nanotechnology