Journal of Stem Cell Research & Therapy

Carboxyl-functionalized polyurethane nanoparticles exhibit immunosuppressive properties via autophagy activation

4^th International Conference and Exhibition on Cell & Gene Therapy

August 10-12, 2015 London, UK

Yen-Jang Huang

Posters-Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Surface functionalization of nanoparticles (NPs) plays the dominant roles in biomedical applications. However, NPs may
induce oxidative stress and inflammation to reduce the application efficiency and injure the biological system, but the
mechanisms are not completely understood. In the recent years, biodegradable polyurethane (PU) has gained attention in
many biomedical fields because of its unique structure of microphase separation, excellent elasticity, and blood compatibility.
Here, we demonstrate that the polyurethane nanoparticles (PU NPs) with distinct surface COO- contents modulate the
immune responses in macrophages. We observed that macrophages dramatically reduced response to LPS for the mRNA
expressions of IL-1β, IL-6, and TNF-α with carboxyl-modified PU NPs, not with amino-modified PU NPs, suggesting a robust
anti-proinflammatory response occurred after PU NP treatment. PU NPs with more carboxyl-modification adsorbed more
extracellular calcium and transported into cells. The cytosolic calcium plays a key role in autophagy activation. The increased
intracellular calcium induced LC3-II protein activation and up-regulation of autophagy related genes, such as autophagy related
5 (ATG5), beclin 1, and cathelicidin. We also observed clear co-localization of autophagosomes and pNF-κB. Furthermore, the
immune suppression of PU NPs was attenuated by incubation with EGTA or Bafilomycin A1. These evidences suggested that
PU NPs reduced the NF-κB-related inflammation via autophagy pathways. The engineered PU NPs with particular surface
modifications may be a platform to realize the biological performance of nanomaterials and to understand how the surface
chemistry of NPs regulates immune responses. Moreover, PU NPs may further be regarded as a promising carrier with drugs
for therapeutic applications of immune-related diseases.

Biography :

Yen-Jang Huang has completed his PhD from National Cheng Kung University, Taiwan and Postdoctoral studies from National Taiwan University, Taiwan. He
specializes in molecular biology, biomaterials and nanomedicine.