Targeted Cancer Theranostics using a Plasmonic Gold Nanohybrid Assembly of a Chiral ligand stabilized Nanorods and Protein Nanoclusters

Abstract

The integration of discrete nanomaterials into a single platform offers an opportunity to synergistically combine the exceptional physicochemical properties of the individual components, which is mainly advantageous in biomedical imaging and therapeutic applications. However, preserving the individual optical features of its constituent nanomaterials during such integration remains a significant confront. In this study, we report the synthesis of a novel hybrid gold nanoplatform, denoted as PEG-PGNC@HA-GNR, comprising the phospholipid polymer conjugate (DSPE-PEG) coated protein gold nanoclusters (PGNCs) and hyaluronic acid (HA) coated anisotropic gold nanorods (GNRs). The gold nanoclusters (GNCs) and GNRs offer distinct optical functionalities, tunable near-infrared (NIR) photoluminescence and efficient photothermal properties respectively. The hybrid nanoarchitecture is meticulously engineered to retain these optical properties, thereby enabling its application as a dual-functional agent for both imaging and photothermal therapy. Chiral, anionic polysaccharide, HA with high affinity for CD44 receptors simultaneously enhanced the biocompatibility of GNRs while imparting plasmon induced chiroptical activity via helical wrapping. PGNCs were coated with DSPE-PEG to enhance biocompatibility, and enable efficient conjugation with HA-GNRs forming a hybrid nanostructure as confirmed by UV-Vis absorption and fluorescence spectroscopy, zeta potential measurements and transmission electron microscopy. The hybrid nanomaterial was carefully engineered to preserve the intrinsic fluorescence of PGNCs to a significant extent even after conjugation with GNRs, and this retention of fluorescence is primarily attributed to the deliberate spatial separation between GNRs and PGNCs which minimises energy transfer interactions. The resulting nanoconjugate displayed distinct circular dichroism (CD) signals and improved photothermal features, offering a dual-functional platform for targeted cancer cell recognition and light-responsive therapy. This strategy highlights the utility of naturally derived chiral ligands in engineering multifunctional, plasmonic nanomaterials for precision oncology. Preliminary in vivo imaging potential of the nanohybrid also has been demonstrated in mice.