April 7, 2025 Dataset Open Access

Exploring Morphology of Thermoplasmonic Nanoparticles to Synergize Immunotherapeutic FAP-positive Cells Sensitization and Photothermal Therapy

Alsadig Ahmed Mohammed, Ahmed; Peng, Xuan; Boutier, Hugo; Rodrigues Loureiro, Liliana Raquel; Feldmann, Anja; Hübner, René; Cabrera, Humberto; Kubeil, Manja; Bachmann, Michael; Baraban, Larysa

The precision of photothermal therapy (PTT) is often hindered by the challenge of achieving selective delivery of thermoplasmonic nanostructures to tumors. Key enabler for the specific delivery is so-called active targeting, leveraging synthetic molecular complexes to address receptors overexpressed by malignant cells. The latter one enables combination of the PTT with other anticancer therapy. In this study, we developed thermoplasmonic nanoconjugates designed to selectively sensitize malignant cells to PTT. These nanoconjugates consist of (i) 20 nm spherical gold nanoparticles (AuNPs) or gold nanostars (AuNSs) as nanocarriers, and facilitate heat-generation upon optical irradiation, and (ii) surface-passivated antibody-based FAP targeting modules (anti-FAP TMs), used in adaptive CAR T-cells immunotherapy. The nanoconjugates demonstrated excellent stability and specific binding to FAP-expressing fibrosarcoma HT1080 (hFAP) cells, as confirmed by immunofluorescence and label-free surface plasmon resonance scattering imaging. Moreover, the nanocarriers showed significant photothermal conversion after visible and near-infrared (NIR) irradiation. Quantitative thermal lens spectroscopy (TLS) 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 properties of the nanocarriers not only streamline nanoparticle delivery, increasing photothermal yield and therapeutic efficacy, but also offers a more comprehensive and potent strategy for cancer treatment with the potential for superior outcomes across multiple modalities.