# Systematic Evaluation of Physicochemical Properties of PEGylated Gold Nanorods Reveals Cell‐Specific Uptake Determinants in Human Immune Cell Subsets

## TL;DR

This study explores how gold nanorods interact with human immune cells, finding that their size, PEG length, and surface charge determine selective targeting and uptake.

## Contribution

The study identifies key physicochemical parameters of AuNR that enable selective targeting of immune cell subsets for nano-immunotherapy.

## Key findings

- Antibody-targeted AuNR selectively bind and induce apoptosis in T-lymphocytes during photothermal therapy.
- PMNs exhibit nonspecific uptake of AuNR, driven by their phagocytic activity.
- Small AuNR size, large PEG size, and near-neutral surface charge reduce non-targeted uptake by PMNs.

## Abstract

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.

This study examines how the physico‐chemical properties of gold nanorods (AuNR) influence their interactions with human immune cells. Antibody‐targeted AuNR selectively bind and induce apoptosis in T‐lymphocytes during photothermal therapy. In contrast, neutrophils have a high intrinsic phagocytic capacity and the design of selective particles requires careful optimization of AuNR size, PEG length, and surface charge.© 2026 WILEY‐VCH GmbH