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Issue 54, 2015
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Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

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Abstract

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. The 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 EC (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 biological 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.

Graphical abstract: Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

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Publication details

The article was received on 07 Mar 2015, accepted on 23 Apr 2015 and first published on 24 Apr 2015


Article type: Paper
DOI: 10.1039/C5RA04057D
Citation: RSC Adv., 2015,5, 43552-43562
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    Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

    S. N. Nadig, S. K. Dixit, N. Levey, S. Esckilsen, K. Miller, W. Dennis, C. Atkinson and A. Broome, RSC Adv., 2015, 5, 43552
    DOI: 10.1039/C5RA04057D

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