Abstract LB-12: Building a novel multifaceted nano-carrier: In vivo and in vitro applications of multifunctional nanolipoprotein particles

Abstract

Abstract We have developed a novel process of production and assembly of nanolipoprotein particles (NLPs) as a multifaceted reagent for cancer imaging, drug delivery, immunomodulation and stabilizing membrane protein complexes for in vitro studies. Nanolipoproteins are components of the human HDL lipoprotein complexes that could be isolated and reconstituted to form NLPs. NLPs are discoidal nanoparticles of 10∼20 nm that self-assemble around a phospholipid bilayer. This bilayer mimics closely the cell membrane can support molecules such as dyes and proteins. NLPs present distinct advantages in terms of particle size, monodispersity and consistency: the circular protein belt constrains the dimensions of the bilayer and ensures NLP particle size distributions can be monodispersed and consistent between preparations. We have demonstrated when targeting agents and imaging agents are attached to the NLPs, they were able to accumulate at the tumor region and can be used for tumor imaging; We also managed to conjugate recombinant IL2 to NLPs. Our data showed that IL2-NLP conjugates were able to stimulate immunomodulation in mice both in vivo and in vitro. NLPs also have shown great promise for solubilizing and characterizing membrane proteins and may make many more membrane protein related complexes accessible for biophysical and biochemical study. Our approach represents a unique solution to the challenge of generating soluble and functional polytopic membrane proteins, facilitating the structural and functional characterization, providing a platform for high-throughput drug screening, and potentially a new type of carrier for tumor imaging and drug delivery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-12. doi:1538-7445.AM2012-LB-12