Engineering the Bio-Nano Interface Using a Multifunctional Coordinating Polymer Coating

In the past three decades, interest in using nanoparticles as diagnostic tools to interrogate various biosystems has witnessed remarkable growth. For instance, it has been shown that nanoparticle probes enable the study of cellular processes at the single molecule level. These advances provide new opportunities for understanding fundamental problems in biology, innovation in medicine, and the treatment of diseases. A multitude of nanoparticles have been designed to facilitate in vitro or in vivo sensing, imaging, and diagnostics. Some of those nanoparticle platforms are currently in clinical trials or have been approved by the U.S. Food and Drug Administration. Nonetheless, using nanoparticles in biology is still facing several obstacles, such as poor colloidal stability under physiological conditions, nonspecific interactions with serum proteins, and low targeting efficiency in biological fluids, in addition to issues of uncontrolled biodistribution and cytotoxicity. All these problems are primarily controlled by the surface stabilizing coating used.In this Account, we summarize recent progress made in our laboratory focused on the development of multifunctional polymers as coordinating ligands, to tailor the surface properties of nanoparticles and facilitate their application in biology. We first detail the advantageous features of the coating strategy, followed by a discussion of the key parameters in the ligand design. We then describe the synthesis and use of a series of multicoordinating polymers as ligands optimized for coating quantum dots (QDs), gold nanoparticles (AuNPs), and magnetic nanoparticles (MNPs), with a focus on (i) how to improve the colloidal stability and antifouling performance of materials in biological conditions; (ii) how to design highly compact coating, without compromising colloidal stability; and (iii) how to tailor the surface functionalities to achieve conjugation to target biomolecules. We also highlight the ability of a phase transfer strategy, mediated by UV irradiation, to promote rapid ligand exchange while preserving the integrity of key functional groups. We then summarize the bioconjugation approaches applied to polymer-coated nanoparticles, with emphasis on the ability of metal-histidine self-assembly and click chemistry, to control the final nanoparticle bioconjugates. Finally, we demonstrate the use of polymer-coated nanoparticles for sensor design based on redox-active interactions and peptide-mediated intracellular delivery. We anticipate that the coating design presented in this Account would advance the integration of nanoparticles into biology and medicine.