Nanotechnological Approaches to Immunosuppression and Tolerance Induction

Abstract

Purpose of review Several preclinical studies have engineered nanoparticles for immune regulation, and have shown promising results in the fields of autoimmunity and cancer. In solid organ transplantation, the use of nanoparticle-based immune regulation has only just begun to emerge but holds significant promise for the improvement of our current standard of care immunosuppressive regimens. In this review, we will shed light on the current status of nanoparticle-engineered immunotherapeutics, and the potential application of these technologies to the field of organ transplantation. Further we discuss different strategies for delivery and potential cellular targeting moieties that could be utilized to obviate the need for high dose systemic immunosuppressive regimens. Recent Findings Recent studies have shown the potential of immunosuppressive laden nanoparticles to increase bioavailability, drug release, and specifically target immune cell compartments as methods to provide recipient immunosuppressive sparing strategies. Summary Nanoparticle centered immunosuppressive strategies hold the potential to usher in a new era in transplant recipient management and could hold the key to minimizing off-target effects of immunosuppressants, along with prolonging transplant survival.

PLGA-Based Composites for Various Biomedical Applications

“…Spray-drying [3,8,24,66,68,69] -Encapsulates hydrophobic and hydrophilic agents. -Fast, convenient and few processing parameters.…”

Macrophages in Organ Transplantation

“…The HDL-based nanobiologics preferentially targeted myeloid cells and promoted M2 regulatory macrophage polarization, which resulted in prevention alloreactive CD8 T cell-mediated immunity and expansion of Treg (155). As a result, we believe that nanobiologics-based delivery of immunotherapeutic agents has great potential in organ transplantation as they improve the pharmacokinetics, minimize the off-target effects, maximize its dosage at the site of action, and can be as used as controlled release systems in a spatiotemporal manner (156). Taken together, it has become evident that the in vivo manipulation of macrophages through the use of nanobiologics represents a promising strategy for long-term allograft survival.…”

Nanodelivery of Mycophenolate Mofetil to the Organ Improves Transplant Vasculopathy

“…The potential to use ISA-loaded nanocarriers (ISA-NP) for targeted drug delivery has begun to attract considerable attention in the field of transplantation. 12,23,24,87,88 Based on the model described here, we speculate that perfusing organs with ISA-NP using currently available perfusion machines could be a readily translatable strategy that could reduce early intragraft inflammation significantly, decrease alloimmune activation, and potentially improve longer-term outcomes. Such findings are supported by previous publications from others.…”