Nanoparticles (NPs) derived from amphiphilic polymers demonstrate great advantages in addressing critical problems in biomedical and pharmaceutic studies. However, their clinical applications are hardly realized. Among the many issues, the immunogenicity of the NPs remains one of the most prominent bottlenecks. Studies suggested that the hydrophobicity of the NP could the primary cause for the immunogenicity.[1-3] Thereby, most NP design involves the use of a camouflage, often, hydrophilic polyethylene glycol (PEG), to protect the hydrophobic component. However, despite the use of camouflages, the NPs can still be identified by the immune systems. Recent studies suggested biomolecules can develop mechanisms to penetrate, highlighting the importance of using biocompatible polymers as the hydrophobic component. We hypothesized that if biocompatible carbohydrate-based polymers was used as the hydrophobic component, NPs with low immunogenicity may be achieved.