Nanosystem for targeting Treg in vivo

M. Bottini, C. Sacchetti, N. Rapini, N. Rosato, A. Magrini, N. Bottini
Sanford Burnham Medical Research Institute, US

Keywords: regulatory T cell, carbon nanotubes, targeting, delivery system, siRNA

Summary:

Due to their ability to suppress the activity of autoreactive cells, “natural” CD4+ CD25high FoxP3+ T cells (Treg) are important drug targets for autoimmune diseases and malignancies. Immunological studies are revealing a growing subset of genes, which are able to affect Treg function and could be targeted for novel therapies. However one major obstacle to the development of Treg-targeted therapies is the lack of approaches able to ensure selective delivery of drugs into these cells. Herein we reported our results about the fabrication of a nanosystem based on PEG-modified carbon nanotubes (PNTs) and aimed at targeting Treg residing in specific tissues. PNTs conjugated with monoclonal antobodies against Treg-enriched markers were able to reach the nucleus of Treg residing in the spleen of healthy mice or in a disease-associated microenvironment (B16 melanoma or arthritic joints) following systemic administration. Moreover, Treg-targeted PNTs were able to deliver siRNA specifically into Treg in vivo. Our data demonstrated that PNT-based nanosystems could open new avenues for the prevention/therapy of autoimmune diseases and malignancies based on the Treg-specific tuning of molecular pathways.