title: Multifunctional porous silicon nanoparticles for cancer theranostics.
abstract: Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy. Radiolabeling of the developed system with (111)In enabled the monitoring of the in vivo biodistribution of the nanocarrier by single photon emission computed tomography (SPECT) in an ectopic PC3-MM2 mouse xenograft model. Fluorescent labeling with Alexa Fluor 488 was used to determine the long-term biodistribution of the nanocarrier by immunofluorescence at the tissue level ex vivo. Modification of the PSi NPs with an iRGD peptide enhanced the tumor uptake of the NPs when administered intravenously. After intratumoral delivery the NPs were retained in the tumor, resulting in efficient tumor growth suppression with particle-loaded sorafenib compared to the free drug. The presented multifunctional PSi NPs highlight the utility of constructing a theranostic nanosystems for simultaneous investigations of the in vivo behavior of the nanocarriers and their drug delivery efficiency, facilitating the selection of the most promising materials for further NP development.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Mirkka P
authors.initials: MP
authors.lastname: Sarparanta
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.affiliation: Research Programs Unit, Translational Cancer Biology and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Maija L K
authors.initials: ML
authors.lastname: Hyvönen
authors.affiliation: Research Programs Unit, Translational Cancer Biology and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Pirjo M
authors.initials: PM
authors.lastname: Laakkonen
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: anu.airaksinen@helsinki.fi.
authors.forename: Anu J
authors.initials: AJ
authors.lastname: Airaksinen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008819:Mice, Nude; D053758:Nanoparticles; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D012825:Silicon / Q000627:therapeutic use*; D000077157:Sorafenib; D000068936:Theranostic Nanomedicine
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D012825:Silicon
keywords: Cancer therapy; Porous silicon nanoparticles; Surface multifunctionalization; Targeting drug delivery; Theranostics