Exploring Morphology of Thermoplasmonic Nanoparticles to Synergize Immunotherapeutic Fibroblast Activation Protein‐Positive Cell Sensitization and Photothermal Therapy

The precision of photothermal therapy (PTT) is often hindered by the challenge of achieving selective delivery of thermoplasmonic nanostructures to tumors. Active targeting, which leverages synthetic molecular complexes to address receptors overexpressed by malignant cells, enables such specificity and facilitates the combination of the PTT with other anticancer therapies. In this study, we developed thermoplasmonic nanoconjugates consisting of (i) 20 nm spherical gold nanoparticles (AuNPs) or gold nanostars (AuNSs) as nanocarriers, and (ii) surface-passivated antibody-based fibroblast activation protein (FAP)-targeting modules, used in adaptive chimeric antigen receptor T-cells immunotherapy. The nanoconjugates demonstrated excellent stability and specific binding to FAP-expressing fibrosarcoma HT1080 genetically modified to express human FAP, as confirmed by fluorescence activated cell sorting, immunofluorescence, and surface plasmon resonance scattering imaging. Moreover, the nanocarriers showed significant photothermal conversion after visible and near-infrared irradiation. Quantitative thermal lens spectroscopy demonstrated the superior photothermal capability of AuNSs, achieving up to 1.5-fold greater thermal enhancement than AuNPs under identical conditions. This synergistic approach, combining targeted immunotherapy with the thermoplasmonic nanocarriers, not only streamlines nanoparticle delivery, increasing photothermal yield and therapeutic efficacy but also offers a comprehensive and potent strategy for cancer treatment with the potential for superior outcomes across multiple modalities.