title: Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms.
abstract: Nanoparticles (NPs) have been suggested for immunotherapy applications in order to optimize the delivery of immuno-stimulative or -suppressive molecules. However, low attention towards the impact of the NPs' physicochemical properties has presented a major hurdle for developing efficient immunotherapeutic agents. Here, the effects of porous silicon (PSi) NPs with different surface chemistries were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes in order to highlight the importance of the NPs selection in immuno-stimulative or -suppressive treatment. Although all the PSi NPs showed high biocompatibility, only thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) NPs were able to induce very high rate of immunoactivation by enhancing the expression of surface co-stimulatory markers of the MDDCs (CD80, CD83, CD86, and HLA-DR), inducing T-cell proliferation, and also the secretion of interleukins (IL-1β, IL-4, IL-6, IL-10, IL-12, IFN-γ, and TNF-α). These results indicated a balanced increase in the secretion of Th1, Th2, and Treg cytokines. Moreover, undecylenic acid functionalized THCPSi, as well as poly(methyl vinyl ether-alt-maleic acid) conjugated to (3-aminopropyl)triethoxysilane functionalized thermally carbonized PSi and polyethyleneimine conjugated undecylenic acid functionalized THCPSi NPs showed moderate immunoactivation due to the mild increase in the above-mentioned markers. By contrast, thermally carbonized PSi (TCPSi) and (3-aminopropyl)triethoxysilane functionalized TCPSi NPs did not induce any immunological responses, suggesting that their application could be in the delivery of immunosuppressive molecules. Overall, our findings suggest all the NPs containing more nitrogen or oxygen on the outermost backbone layer have lower immunostimulatory effect than NPs with higher C-H structures on the surface.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland. Electronic address: m.a.shahbazi@helsinki.fi.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Malaga Hospital, UMA, Málaga, Spain.
authors.forename: Tahia D
authors.initials: TD
authors.lastname: Fernández
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland; Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014, University of Turku, Finland.
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.affiliation: Therapeutic Nanosystem, The Andalusian Centre for Nanomedicine and Biotechnology, BIONAND, Málaga, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Guével
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Malaga Hospital, UMA, Málaga, Spain.
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Malaga Hospital, UMA, Málaga, Spain.
authors.forename: Martti H
authors.initials: MH
authors.lastname: Kaasalainen
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Malaga Hospital, UMA, Málaga, Spain.
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland.
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D016062:Porosity; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D012825:Silicon / Q000737:chemistry* / Q000494:pharmacology*; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D015850:Interleukin-6; D011437:Propylamines; D012821:Silanes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D011094:Polyethyleneimine; C477625:amino-propyl-triethoxysilane; D012825:Silicon
keywords: Co-stimulatory signal; Immune response; Interleukins; Monocyte-derived dendritic cells; Porous silicon nanoparticles; T-cell proliferation