Cellular and molecular targeting for nanotherapeutics in transplantation tolerance

Abstract

The induction of donor-specific tolerance to transplanted cells and organs, while preserving immune function as a whole, remains a highly sought after and elusive strategy for overcoming transplant rejection. Tolerance necessitates modulating a diverse array of cell types that recognize and respond to alloantigens, including antigen presenting cells and T lymphocytes. Nanotherapeutic strategies that employ cellular and biomaterial engineering represent an emerging technology geared towards the goal of inducing transplant tolerance. Nanocarriers offer a platform for delivering antigens of interest to specific cell types in order to achieve tolerogenic antigen presentation. Furthermore, the technologies also provide an opportunity for local immunomodulation at the graft site. Nanocarriers delivering a combination of antigens and immunomodulating agents, such as rapamycin, provide a unique technology platform with the potential to enhance outcomes for the induction of transplant tolerance.

Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

“…diseases, embodying the potential to either enhance (e.g., conditions such as malignancy/vaccination) or suppress effector activity (e.g., transplantation or autoimmunity) as required (39)(40)(41)(42)(43)(44)(45)(46). While the vast majority of these efforts have relied on transmission via absorption through the skin, targeted delivery to HEVs via…”

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

“…Sadly, however, recipients of allogeneic islet grafts require lifelong immunosuppression to avoid host rejection of the transplanted cells [3, 46]. Our group and collaborators have explored the use of negatively charged antigen-coupled or encapsulating nanoparticles to induce tolerance in transplant models [122] and have used ECDI-treated donor splenocytes to tolerize recipients of islet transplants [124•]. A recent study investigated the feasibility of using donor antigen-coupled PLG nanoparticles in place of apoptotic cells.…”

“…a Nanoparticles targeting APCs. Top : MARCO receptor dependent uptake of antigen-coupled and antigen-encapsulating PLG [98•, 116••, 117••, 118••, 119•, 120••, 121•, 122]. Middle : PLG encapsulating both antigen and rapamycin [109, 110].…”

Tolerogenic Nanoparticles Impacting B and T Lymphocyte Responses Delay Autoimmune Arthritis in K/BxN Mice

“…Another approach aimed at treating ongoing immune responses involves targeting of antigen experienced T cells with peptide-MHC bound nanoparticles to induce T regulatory cells (Tregs), but this technology requires knowledge of the precise peptide antigen recognized by the T cells 27 28 . Other approaches seek to program T cells through antigen-presenting cells (APCs) presented with antigen coupled to syngeneic cells 29 30 , or synthetic particles carrying antigens and/or immune-modulators [31][32][33][34][35][36][37][38] . The general strategy is to create tolerogenic APCs that secrete cytokines to induce antigen-specific anergy/deletion of T cells, or reprogram them to Tregs 10 11 27 .…”