Hybrid red blood cell membrane coated porous silicon nanoparticles functionalized with cancer antigen induce depletion of T cells

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimickingblockcopolymer polydimethylsiloxane-b-poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4+and cytotoxic CD8+T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases. A. R. acknowledges financial support from the Finnish Cultural Foundation. H. A. S. acknowledges financial support from the University of Helsinki Research Funds, the Sigrid Juselius Foundation, the HiLIFE Research Funds, the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013; Grant No. 310892) and European Research Council Proof-of-Concept Grant (Decision No. 825020). The authors acknowledge the following core facilities funded by Biocenter Finland: Electron Microscopy Unit of the University of Helsinki for providing the facilities for TEM imaging and the Flow Cytometry Unit for providing the facilities for FACS experiments, and Nanomicroscopy Center of Aalto University for providing the facilities for the cryo-TEM imaging. A. R. acknowledges ¿nancial support from the Finnish Cultural Foundation. H. A. S. acknowledges ¿nancial support from the University of Helsinki Research Funds, the Sigrid Juselius Foundation, the HiLIFE Research Funds, the European Research Council under the European Union's Seventh Frame-work Programme (FP/2007–2013; Grant No. 310892) and European Research Council Proof-of-Concept Grant (Decision No. 825020). The authors acknowledge the following core facilities funded by Biocenter Finland: Electron Microscopy Unit of the University of Helsinki for providing the facilities for TEM imaging and the Flow Cytometry Unit for providing the facilities for FACS experiments, and Nanomicroscopy Center of Aalto University for providing the facilities for the cryo-TEM imaging.