Murine and Non-Human Primate Dendritic Cell Targeting Nanoparticles for in Vivo Generation of Regulatory T-Cells

作者：Stead Sebastian O; Kireta Svjetlana; McInnes Steve J P; Kette Francis D; Sivanathan Kisha N; Kim Juewan; Cueto Diaz Eduardo J; Cunin Frederique; Durand Jean Olivier; Drogemuller Christopher J; Carroll Robert P; Voelcker Nicolas H^*; Coates Patrick T^*

来源：ACS Nano, 2018, 12(7): 6637-6647.

DOI：10.1021/acsnano.8b01625

• rapamycin
• regulatory T-cells
• nanoparticles
• porous silicon
• nanomedicine
• tolerance
• DC-SIGN

Porous silicon nanoparticles (pSiNP), modified to target dendritic cells (DC), provide an alternate strategy for the delivery of immunosuppressive drugs. Here, we aimed to develop a DC-targeting pSiNP displaying c-type lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and CD11c monoclonal antibodies. The in vivo tracking of these fluorescent DC-targeting nanoparticles was assessed in both C57BL/6 mice and common marmosets (Callithrix jacchus) by intravenous injection (20 mg/kg). Rapamycin and ovalbumin (OVA)(323-339) peptide loaded pSiNP were employed to evaluate their ability to generate murine CD4(+)CD25(+)FoxP3(+) regulatory T-cells in vivo within OVA sensitized mice. In vivo, pSiNP migrated to the liver, kidneys, lungs, and spleen in both mice and marmosets. Flow cytometry confirmed pSiNP uptake by splenic and peripheral blood DC when functionalized with targeting antibodies. C57BL/6 OVA sensitized mice injected with CD11c-pSiNP loaded with rapamycin + OVA(323-339) produced a 5-fold higher number of splenic regulatory T-cells compared to control mice, at 40 days post-pSiNP injection. These results demonstrate the importance of the immobilized targeting antibodies to enhance cellular uptake and enable the in vivo generation of splenic regulatory T-cells.

• 出版日期2018-7