Systematic Evaluation of Physicochemical Properties of PEGylated Gold Nanorods Reveals Cell-Specific Uptake...

Gold nanorods (AuNR) are multifunctional transducers applied in heat-ablating cancer therapy, bio-imaging, and controlled drug release. Despite extensive studies of AuNR interactions with cancer cells, the AuNR characteristics that determine their interaction with primary human immune subsets remain poorly characterized. Here, we investigated the effect of AuNR physico-chemical properties on the binding, uptake, and cell death responses by human T-lymphocytes and polymorphonuclear neutrophils (PMNs). We demonstrate that antibody targeting with α-CD3-AuNR conjugates results in selective binding of AuNR to T-lymphocytes. Photothermal therapy (PTT) using these AuNR triggered apoptotic pathways and evoked selective cell death in T-lymphocytes. In contrast, PMN exhibited nonspecific target-independent uptake, consistent with their inherent phagocytic activity. We evaluated the AuNR size, PEG molecular weight, and surface charge (zeta potential, ζ) as parameters of uptake by PMN and identified small AuNR size, large PEG size, and near-neutral surface charge as the crucial parameters that reduce non-targeted uptake of AuNR by PMN. This design and development of AuNR-based immunotherapeutics demonstrates that PTT in primary human immune cells requires cellular subset-specific AuNR design. We identify key AuNR properties that drive their interactions with human immune cells and have implications for the translation of experimental and preclinical work into future nano-immunotherapies.