Mannosylated dextran nanoparticles: A pH-sensitive system engineered for immunomodulation through mannose targeting
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AbstractBiotherapeutic delivery is a rapidly growing field in need of new materials that are easy to modify, are biocompatible, and provide for triggered release of their encapsulated cargo. Herein, we report on a particulate system made of a polysaccharide-based pH-sensitive material that can be efficiently modified to display mannose-based ligands of cellsurface receptors. These ligands are beneficial for antigen delivery, as they enhance internalization and activation of APCs, and are thus capable of modulating immune responses. When compared to unmodified particles or particles modified with a nonspecific sugar residue used in the delivery of antigens to dendritic cells (DCs), themannosylated particles exhibited enhanced antigen presentation in the context of major histocompatibility complex (MHC) class I molecules. This represents the first demonstration of a mannosylated particulate system that enables enhancedMHC I antigen presentation by DCs in vitro. Our readily functionalized pH-sensitive material may also open new avenues in the development of optimally modulated vaccine delivery systems. © 2011 American Chemical Society.
SponsorsThis research was funded through the Frechet "various gifts" fund for the support of research in new materials. We also thank Ann Fischer in the U.C. Berkeley Cell Culture Facility for her help with cell culture preparation, Dr. Valentin Rodionov for providing ligand used in CuAAC reactions, and Dr. Chris Canlas and Dr. Eric M. Bachelder for helpful discussions.
PublisherAmerican Chemical Society (ACS)
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