title: Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo.
abstract: Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min. Furthermore, accumulation of the coated particles was mainly taking place in the spleen whereas uncoated nanoparticles were rapidly deposited in the liver. The protein coronas of the particles differed considerably from each other. The uncoated particles had substantially more proteins adsorbed including liver and immune active proteins, whereas the coated particles had proteins capable of suppressing cellular uptake. These reasons along with agglomeration observed in blood circulation were concluded to cause the differences in the behavior in vivo. The biofate of the particles was monitored with magnetic resonance imaging by incorporating superparamagnetic iron oxide nanocrystals inside the pores of the particles making dynamic imaging of the particles feasible. The results of the present study pave the way for further development of the porous inorganic delivery system in the sense of active targeting as the carriers can be easily chemically modified allowing also magnetically targeted delivery and diagnostics.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nissinen
authors.forename: Simo
authors.initials: S
authors.lastname: Näkki
authors.forename: Hanne
authors.initials: H
authors.lastname: Laakso
authors.affiliation: Institute of Biochemistry, Vilnius University , Saulėtekio al. 7, LT-10257 Vilnius, Lithuania.
authors.forename: Dalius
authors.initials: D
authors.lastname: Kučiauskas
authors.affiliation: Institute of Biochemistry, Vilnius University , Saulėtekio al. 7, LT-10257 Vilnius, Lithuania.
authors.forename: Algirdas
authors.initials: A
authors.lastname: Kaupinis
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.affiliation: Imaging Centre, Kuopio University Hospital , Puijonlaaksontie 2, FI-70210 Kuopio, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Liimatainen
authors.forename: Mervi
authors.initials: M
authors.lastname: Hyvönen
authors.affiliation: Institute of Biochemistry, Vilnius University , Saulėtekio al. 7, LT-10257 Vilnius, Lithuania.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Valius
authors.forename: Olli
authors.initials: O
authors.lastname: Gröhn
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D000818:Animals; D001769:Blood / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D000066970:Protein Corona / Q000737:chemistry* / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D012825:Silicon / Q000097:blood / Q000737:chemistry / Q000633:toxicity; D013154:Spleen / Q000378:metabolism
chemical_list: D020099:Coated Materials, Biocompatible; D000066970:Protein Corona; D011092:Polyethylene Glycols; D012825:Silicon
keywords: MRI; circulation time; corona proteomics; inorganic drug carrier; intravenous administration; nanoparticle; porous silicon