Targeted cancer theranostics using a plasmonic gold nanohybrid assembly of chiral ligand stabilized nanorods and protein nanoclusters

Abstract

The integration of discrete nanomaterials into a single platform enables the synergistic combination of their exceptional physicochemical properties, which is particularly advantageous for biomedical imaging and therapy. However, retaining the intrinsic optical features of individual components during such integration remains a major challenge. In particular, understanding the interactions between metallic nanostructures with distinct functionalities continues to be of significant scientific interest. In this study, we report the design of a novel hybrid gold nanoplatform, PEG–PGNC@HA–GNR, comprising DSPE–PEG coated protein gold nanoclusters (PGNCs) and hyaluronic acid (HA) wrapped anisotropic gold nanorods (GNRs). The PGNCs exhibit tunable near-infrared (NIR) photoluminescence, while GNRs provide efficient photothermal property. The hybrid nanoarchitecture was meticulously engineered to preserve these complementary optical features, enabling dual functionality for imaging and photothermal therapy. HA, a chiral anionic polysaccharide with high affinity for CD44 receptors, simultaneously enhanced GNR biocompatibility and induced plasmon driven chiroptical activity via helical wrapping. DSPE–PEG coating on PGNCs improved stability and facilitated their conjugation with HA–GNRs, yielding a hybrid nanostructure validated by UV-Vis and fluorescence spectroscopy, zeta potential analysis and TEM. The hybrid retained significant PGNC fluorescence despite conjugation with GNRs, largely due to deliberate spatial separation minimizing energy transfer. The resulting construct displayed distinct circular dichroism (CD) signals and enhanced photothermal performance, offering a multifunctional platform for targeted cancer recognition and light-triggered therapy. Preliminary in vivo studies further demonstrated its imaging potential in mice. This work underscores the utility of naturally derived chiral ligands in engineering multifunctional plasmonic nanomaterials for precision oncology.