Functionalized Nanoparticles with Long‐Term Stability in Biological Media

Abstract

Nanoparticles have been extensively studied in recent years due to their unique optical, magnetic, or chemical properties.[1-4] While many synthetic methods have been investigated, an effective way to produce ultrafine and monodisperse nanoparticles with controllable sizes is thermal decomposition of precursors in organic solvents at high temperature.[5,6] In this approach, nanoparticles are stabilized by hydrophobic coatings and as a result, the as-synthesized nanoparticles can not be dispersed in aqueous solutions. In biomedical applications, nanoparticles have to be hydrophilic and maintain a superior stability in biological media. For advanced biomedical applications of nanoparticles (e.g., in vivo diagnostics and therapy), additional requirements such as minimization of non-specific uptake by reticulo-endothelial systems (RES) must be imposed in order to achieve long blood circulation time and high diagnostic or therapeutic efficiency.[7] In addition, the surface of the nanoparticle should possess functional groups for further conjugation of targeting ligand or therapeutic agents. Commonly used modification strategies for coating hydrophobic nanoparticles with hydrophilic polymers include ligand exchange,[8] micelle encapsulation,[9] and covalent bonding.[10] [11] Particularly, hydrophilic poly(ethylene glycol) (PEG) have been the focus of research as an effective coating materials for nanoparticles[2,12-15] due to its ability to resist protein fouling and provide steric hindrance preventing nanoparticle from aggregation.[12,16,17] Typical examples include coating PEG on hydrophobic nanoparticles via ligand exchange in which dopamine linked PEG replaces oleylamine & oleic acid on the particle[18] and coating PEG on iron oxide nanoparticles in situ via covalent bonding during the aqueous co-precipitation process.[10] Despite the advances made with those methods, the challenge remains in producing a highly stable polymeric coating on nanoparticles and retaining the long-term stability of functionalized nanoparticles in biological-relevant media.