Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection <i>in vivo</i>

Zhu, Peng; Atkinson, Carl; Dixit, Suraj; Cheng, Qi; Tran, Danh; Patel, Kunal; Jiang, Yulin; Esckilsen, Scott; Miller, Kayla; Bazzle, G.; Allen, Patterson; Moore, Alfred; Broome, Ann-Marie; Nadig, Satish N.

doi:10.1039/c8ra01555d

Cited by 19 publications

(24 citation statements)

References 31 publications

(64 reference statements)

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“…For instance, the modification of antibodies on PLGA NPs successfully moderated the chronic rejection of transplanted heart by targeting IL-6 secreted by allograft-derived dendritic cells (ADDCs) (Solhjou et al, 2017 ). Furthermore, the endothelial cell inflammation and pro-inflammatory cytokines secretion following tracheal or aortic allografts could be greatly attenuated by the pre-treatment of rapamycin (Nadig et al, 2015 ; Zhu et al, 2018 ).…”

Section: Alternative Strategies For Iri Therapy and Organ Transplantamentioning

confidence: 99%

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

Chen

2020

Front. Chem.

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Ischemia-reperfusion injury (IRI) is a severe condition for most organs, which could occur in various tissues including brain, heart, liver, and kidney, etc. As one of the major hazards, reactive oxygen species (ROS) is excessively generated after IRI, which causes severe damage inside tissues and further induces the following injury via inflammatory response. However, current medical strategies could not thoroughly diagnose and prevent this disease, eventually leading to severe sequelae by missing the best time point for therapy. In the past decade, various nanoparticles that could selectively respond to ROS have been developed and applied in IRI. These advanced nanomedicines have shown efficient performance in detecting and treating a series of IRI (e.g., acute kidney injury, acute liver injury, and ischemic stroke, etc.), which are well-summarized in the current review. In addition, the nano-platforms (e.g., anti-IL-6 antibody, rapamycin, and hydrogen sulfide delivering nanoparticles, etc.) for preventing IRI during organ transplantation have also been included. Moreover, the development and challenges of ROS-responsive nanomedicine are systematically discussed for guiding the future direction.

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Section: Alternative Strategies For Iri Therapy and Organ Transplantamentioning

confidence: 99%

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

Chen

2020

Front. Chem.

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“…In vitro tests by MTT showed no cytotoxicity of empty micelles, loaded with rapamycin (targeted or untargeted), or free rapamycin up to concentrations of 3 μg/ml after 6 h. Additionally, in vitro targeting demonstrated, and inflammatory markers (IL-6 and IL-8) were decreased; these results were confirmed in a C57 mouse model [77]. This same group recently provided evidence that this targeted formulation could be used as an additive and pretreatment regimen to prevent chronic rejection in vivo [78].…”

Section: Rapamycinmentioning

confidence: 83%

The Hurdles of Nanotoxicity in Transplant Nanomedicine

Nagy

Robbins

2019

Nanomedicine (Lond.)

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Nanomedicine has matured significantly in the past 20 years and a number of nanoformulated therapies are cleared by regulatory agencies for use across the globe. Transplant medicine is one area that has significantly benefited from the advancement of nanomedicine in recent times. However, while nanoparticle-based therapies have improved toxicological profiles of some drugs, there are still a number of aspects regarding the biocompatibility and toxicity of nanotherapies that require further research. The goal of this article is to review toxicological profiles of immunosuppressant therapies and their conversion into nanomedicine formulations as well as introduce future challenges associated with current in vitro and in vivo toxicological models.

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“…This study further demonstrated that during cold preservation for 4-6 h, receptor-mediated endocytosis of rapamycin-loaded micelles can potentially reduce the secretion of inflammatory cytokines. 49 Collectively, these studies demonstrate that during standard allograft procurement procedures, endothelial cells of the allografts can be readily targeted by NPs to reduce post-transplant allograft injury and potentially promote long-term allograft survival.…”

Section: Nanotechnology For Promoting Long-term Transplant Survivalmentioning

confidence: 88%

“…47 Employing normothermic machine perfusion of human kidneys, Tietjen et al 48 demonstrated that endothelial cells could be targeted by an anti-CD31 antibody conjugated to poly(lactic acid)-poly (ethylene) glycol NPs. In another recent study, Zhu et al 49 demonstrated that incubating mouse tracheal and aortic allografts with rapamycin-loaded polyethylene glycol micelles (10 nM in size) in standard hypothermic University of Wisconsin (UW) solution significantly prevents the chronic rejection of these allografts post-transplantation. This study further demonstrated that during cold preservation for 4-6 h, receptor-mediated endocytosis of rapamycin-loaded micelles can potentially reduce the secretion of inflammatory cytokines.…”

Section: Nanotechnology For Promoting Long-term Transplant Survivalmentioning

confidence: 99%

Emerging approaches and technologies in transplantation: the potential game changers

Dangi

Luo

2019

Cell Mol Immunol

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Newly emerging technologies are rapidly changing conventional approaches to organ transplantation. In the modern era, the key challenges to transplantation include (1) how to best individualize and possibly eliminate the need for lifelong immunosuppression and (2) how to expand the donor pool suitable for human transplantation. This article aims to provide readers with an updated review of three new technologies that address these challenges. First, single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to transplantation. The new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants, as well as exciting new molecular signatures involved in alloimmune responses. Second, sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant tolerance. Tolerogenic nanoparticles with regulatory molecules and donor antigens are capable of targeting host immune responses with tremendous precision, which, in some cases, results in donor-specific tolerance. Third, CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory molecules. This technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human organs. Collectively, these new technologies are positioning the transplant community for major breakthroughs that will significantly advance transplant medicine.

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Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

Abstract: (a) Rapamycin nanotherapeutic pre-treatment improves tracheal allograft outcome after transplantation. (b) Nanotherapy reduces aortic allograft vasculopathy. (c) Dose dependency of the nanotherapy in aortic interposition allografts.

Cited by 19 publications

References 31 publications

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

The Hurdles of Nanotoxicity in Transplant Nanomedicine

Emerging approaches and technologies in transplantation: the potential game changers

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