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Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model.

Publication ,  Journal Article
Shah, S; Daneshmandi, S; Hughes, KR; Yu, S; Bedoya, AM; Shea, LD; Luo, X
Published in: Biomaterials
July 2019

A robust regimen for inducing allogeneic transplantation tolerance involves pre-emptive recipient treatment with donor splenocytes (SP) rendered apoptotic by 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide(ECDI) treatment. However, such a regimen is limited by availability of donor cells, cost of cell procurement, and regulatory hurdles associated with cell-based therapies. Nanoparticles (NP) delivering donor antigens are a promising alternative for promoting transplantation tolerance. Here, we used a B6.C-H-2bm12(bm12) to C57BL/6(B6) skin transplant model involving a defined major histocompatibility antigen mismatch to investigate design parameters of poly(lactide-co-glycolide) (PLG) NPs delivering peptides containing the donor antigen for optimizing skin allograft survival. We showed that an epitope-containing short peptide (P1) was more effective than a longer peptide (P2) at providing graft protection. Importantly, the NP and P1 complex (NP-ECDI-P1) resulted in a significant expansion of graft-infiltrating Tregs. Interestingly, in comparison to donor ECDI-SP that provided indefinite graft protection, NP-ECDI-P1 targeted different splenic phagocytes and skin allografts in these recipients harbored significantly more graft-infiltrating CD8+IFN-γ+ cells. Collectively, the current study provides initial engineering parameters for a cell-free and biocompatible NP-peptide platform for transplant immunoregulation. Moreover, it also provides guidance to future NP engineering endeavors to recapitulate the effects of donor ECDI-SP as a goal for maximizing tolerance efficacy of NP formulations.

Duke Scholars

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

July 2019

Volume

210

Start / End Page

70 / 82

Location

Netherlands

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Tolerance
  • Tissue Distribution
  • T-Lymphocytes
  • Skin Transplantation
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Peptides
  • Nanoparticles
  • Mice, Inbred C57BL
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shah, S., Daneshmandi, S., Hughes, K. R., Yu, S., Bedoya, A. M., Shea, L. D., & Luo, X. (2019). Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model. Biomaterials, 210, 70–82. https://doi.org/10.1016/j.biomaterials.2019.04.030
Shah, Sahil, Saeed Daneshmandi, Kevin R. Hughes, Shuangjin Yu, Angela M. Bedoya, Lonnie D. Shea, and Xunrong Luo. “Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model.Biomaterials 210 (July 2019): 70–82. https://doi.org/10.1016/j.biomaterials.2019.04.030.
Shah S, Daneshmandi S, Hughes KR, Yu S, Bedoya AM, Shea LD, et al. Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model. Biomaterials. 2019 Jul;210:70–82.
Shah, Sahil, et al. “Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model.Biomaterials, vol. 210, July 2019, pp. 70–82. Pubmed, doi:10.1016/j.biomaterials.2019.04.030.
Shah S, Daneshmandi S, Hughes KR, Yu S, Bedoya AM, Shea LD, Luo X. Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model. Biomaterials. 2019 Jul;210:70–82.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

July 2019

Volume

210

Start / End Page

70 / 82

Location

Netherlands

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Tolerance
  • Tissue Distribution
  • T-Lymphocytes
  • Skin Transplantation
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Peptides
  • Nanoparticles
  • Mice, Inbred C57BL
  • Male