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Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity.
Nadig, Satish N; Dixit, Suraj K; Levey, Natalie; Esckilsen, Scott; Miller, Kayla; Dennis, William; Atkinson, Carl; Broome, Ann-Marie.
Afiliación
  • Nadig SN; Department of Surgery, Division of Transplant, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. ; Tel: 01 843 792 8596; nadigsn@musc.edu.
  • Dixit SK; Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. ; Tel: 01 843 792 1716; atkinsoc@musc.edu.
  • Levey N; South Carolina Investigators in Transplantation (SCIT), Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. ; Tel: 01 843 792 3553; nadigsn@musc.edu.
  • Esckilsen S; Department of Radiology & Radiological Science, Medical University of South Carolina, 68 President Street MSC 120, Charleston, SC 29425, USA. ; Tel: 01 843 876 2481; broomea@musc.edu.
  • Miller K; Center for Biomedical Imaging (CBI), Medical University of South Carolina, 68 President Street MSC 120, Charleston, SC 29425, USA. ; Tel: 01 843 876 2481; broomea@musc.edu.
  • Dennis W; Department of Surgery, Division of Transplant, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. ; Tel: 01 843 792 8596; nadigsn@musc.edu.
  • Atkinson C; Department of Surgery, Division of Transplant, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. ; Tel: 01 843 792 8596; nadigsn@musc.edu.
  • Broome AM; Department of Radiology & Radiological Science, Medical University of South Carolina, 68 President Street MSC 120, Charleston, SC 29425, USA. ; Tel: 01 843 876 2481; broomea@musc.edu.
RSC Adv ; 5(54): 43552-43562, 2015.
Article en En | MEDLINE | ID: mdl-26167278
In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. Uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac endothelial cell (MCEC) and HUVEC production and release of the pro-inflammatory cytokines, IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biologic tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: RSC Adv Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: RSC Adv Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido