title: Tumour homing peptide-functionalized porous silicon nanovectors for cancer therapy.
abstract: Tumour targeting nanoparticles (NPs) have demonstrated great potential for enhancing anticancer drug delivery to tumour sites and for reducing the side effects of chemotherapy. However, many nanoparticulate delivery systems still lack efficient tumour accumulation. In this work, we present a porous silicon (PSi) nanovector functionalized with a tumour-homing peptide, which targets the mammary-derived growth inhibitor (MDGI) expressing cancer cells both in vitro and in vivo, thereby enhancing the accumulation of the NPs in the tumours. We demonstrated that the tumour homing peptide (herein designated as CooP) functionalized thermally hydrocarbonized PSi (THCPSi) NPs homed specifically to the subcutaneous MDGI-expressing xenograft tumours. The THCPSi-CooP NPs were stable in human plasma and their uptake by MDGI-expressing cancer cells measured by confocal microscopy and flow cytometry was significantly increased compared to the non-functionalized THCPSi NPs. After intravenous injections into nude mice bearing MDGI-expressing tumours, effective targeting was detected and THCPSi-CooP NPs showed ~9-fold higher accumulation in the tumour site compared to the control THCPSi NPs. Accumulation of both NPs in the vital organs was negligible.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Päivi J
authors.initials: PJ
authors.lastname: Kinnari
authors.forename: Maija L K
authors.initials: ML
authors.lastname: Hyvönen
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.forename: Martti H
authors.initials: MH
authors.lastname: Kaasalainen
authors.forename: Antti
authors.initials: A
authors.lastname: Rivinoja
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.forename: Pirjo M
authors.initials: PM
authors.lastname: Laakkonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000327:Adsorption; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D001798:Blood Proteins; D050556:Fatty Acid-Binding Proteins; D010455:Peptides; D012825:Silicon
keywords: Breast cancer; Homing peptide; Nanoparticles; Nanovector; Porous silicon; Tumour targeting