Poly(oxyethylene sugaramide)s: Unprecedented multihydroxyl building blocks for tumor-homing nanoassembly

Hydrogen bonding is a major intermolecular interaction for self-assembly occurring in nature. Here we report novel polymeric carbohydrates, i.e., poly(oxyethylene galactaramide)s (PEGAs), as biomimetic building blocks to construct hydrogen bond-mediated self-assembled nanoparticles that are useful for biomedical in vivo applications. PEGAs were conceptually designed as a biocompatible hybrid between polysaccharide and poly(ethylene glycol) (PEG) to attain multivalent hydrogen bonding as well as fully hydrophilic, non-ionic and antifouling characteristics. It was revealed that PEGAs are capable of homospecies hydrogen bonding in water and constructing multi-chain assembled nanoparticles whose structural integrity is highly stable with varying concentration, temperature and pH. Using near-infrared fluorescence imaging we demonstrate facile blood circulation and efficient tumor accumulation of the self-assembled PEGA nanoparticles that were intravenously injected into mice. These in vivo behaviors elucidate the combined merits of our design strategy, i.e., biocompatible chemical constitution capable of multivalent hydrogen bonding, antifouling properties, minimal cell interaction and mesoscopic colloidal self-assembly, as well as size-motivated tumor targeting.