Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Porous silicon (pSi) nanoparticles, modified to specifically target DC, provide a novel platform to carry and deliver immunosuppressive drugs. The aim was to conjugate DC-SIGN antibodies (DC specific) to rapamycin loaded pSi-nanoparticles and target DC to induce immune regulation. pSi-nanoparticles were functionalised with DC-SIGN mAb (DCSIGN-pSi) and co-cultured with either human monocyte-derived DC (5 days) or whole blood (24h) particle uptake assessed by flow cytometry. Rapamycin loaded, DC-SIGN-pSi treated DC were used as allogeneic stimulators in MLRs to assess their stimulatory capacity. In vivo DC targeting was determined by IV injection of common marmosets (Callithrix jacchus) with targeting (DC-SIGN-pSi) or non-targeting (Isotype-pSi) functionalised, fluorescent pSi-nanoparticles (20mg/kg). After 24h, marmosets were IVIS Lumina imaged to assess particle distribution, whilst flow cytometry was used to determine peripheral blood and splenocytes cellular uptake. DC-SIGN functionalised nanoparticles showed increased uptake by DC in a time- and dose-dependent manner, in vitro. Rapamycin loaded nanoparticles inhibited DC markers CD40, CD80, CD86, CD83 and MHC II expression. Treated DC significantly inhibited allogeneic T-cell proliferation by 50% (n=3; p<0.01) compared to mature DC. Nanoparticles tracked to the liver and kidneys, with a large proportion detected in the lung of some animals. Flow cytometric analysis showed that splenic and peripheral blood marmoset myeloid DC were positive for nanoparticles. Rapamycin loaded nanoparticles functionalised with DC-SIGN mAb provide targeted delivery to DCs in vitro. In vivo we are the first to show the tracking of DC-SIGN-NP in a non-human primate model as a novel way to target DCs in situ.
CITATION INFORMATION: Stead S, Kireta S, McInnes S, Rose P, Jesudason S, Grey S, Rojas-Canales D, Carroll R, Voelcker N, Coates P. DC-SIGN Functionalized Porous Silicon Nanoparticles Targeting to Human and Non-Human Primate Dendritic Cells. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Stead S, Kireta S, McInnes S, Rose P, Jesudason S, Grey S, Rojas-Canales D, Carroll R, Voelcker N, Coates P. DC-SIGN Functionalized Porous Silicon Nanoparticles Targeting to Human and Non-Human Primate Dendritic Cells. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/dc-sign-functionalized-porous-silicon-nanoparticles-targeting-to-human-and-non-human-primate-dendritic-cells/. Accessed July 11, 2020.
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