This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery. We reflect on the physical properties that make NPs advantageous for in vivo efficacy, and review recent advances in major NP based biomedical applications. Critical questions of transport, uptake, and clearance will be discussed and illustrated through the success and opportunities of NP imaging and therapy on a photodynamic therapy (PDT) based NP system that has been developed in our lab over the past decade (540 references).

For over half a century, alternating electric fields have been used to induce particle transport, furnishing the ζ-potential of analytes with sizes ranging from a few nanometers to several micrometers. Concurrent advances in nanotechnology have provided new materials for catalysis, self-assembly, and biomedical applications, all of which benefit from a thorough understanding of particle surface charge. Therefore, the measurement of the ζ-potential via electrophoretic light scattering (ELS) has become essential for nanoparticle (NP) research. However, the interpretation of NP electrophoretic mobility, especially that of ligand-coated NPs, can be a complex undertaking. Despite the inherent intricacy of these data, key concepts from colloidal science can help to distill valuable information from ELS. In this Account, we adopt PEGylated Au NPs as an illustrative example to explore extensions of the classical theories of Smoluchowski, Hückel, and Henry to more contemporary theories for ligand-coated NP systems such as those from Ohshima, and Hill, Saville, and Russel. First, we review the basic experimental considerations necessary to understand NP electrophoretic mobility, identifying when O'Brien and White's numerical solution of the standard electrokinetic model should be adopted over Henry's closed-form analytical approximation. Next, we explore recent developments in the theory of ligand-coated particle electrophoresis, and how one can furnish accurate and meaningful relationships between measured NP mobility, ζ-potential, and surface charge. By identifying key ligand-coated NP parameters (e.g., coating thickness, permeability, molecular mass, and hydrodynamic segment size), we present a systematic method for quantitatively interpreting NP electrophoretic mobility. In addition to reviewing theoretical foundations, we describe our recent results that examine how the unique surface curvature of NPs alters and controls their properties. These data provide guidelines that can expedite the rational design of NPs for advanced uses, such as heterogeneous catalysis and in vivo drug delivery. As a practical demonstration of these concepts, we apply the ligand-coated theory to a recently developed noncovalent PEGylated Au NP drug-delivery system. Our analysis suggests that anion adsorption on the Au NP core may enhance the stability of these NP-drug conjugates in solution. In addition to providing useful nanochemistry insights, the information in this Account will be useful to biomedical and materials engineers, who use ELS and ζ-potentials for understanding NP dynamics.

EGF‐modified Au NP–Pc 4 conjugates showed 10‐fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide‐targeted Au NPs. Compared to the untargeted conjugates, EGF–Au NP–Pc 4 conjugates showed 10‐fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard‐to‐reach cancers.

Electromigration of nanoparticles (NPs) is relevant to many technological and biological applications. We correlate the experimentally observed electromigration of Au NPs with a closed-form theoretical model that furnishes key NP characteristics, including the previously unknown values of Au NP core ζ-potential, PEG-corona permeability, and particle-hydrogel friction coefficient. More generally, the theory furnishes new understanding of NP electromigration in complex environments, establishing a robust and predictive model to guide the design and characterization of functionalized NPs.