In recent years, new approaches have been developed in drug delivery systems to ensure adequate and stable release and to reduce the side effects of the drug [[1], [2], [3], [4]]. In particular, approaches that create a synergistic effect by combining the properties of materials and application methods show promising results in cancer therapy. Among the materials used, bioinspired materials developed from highly biocompatible biomaterials that can be found in nature or human physiology provide unique potential for these synergistic approaches [5,6]. Drug delivery systems consisting of structures such as proteins, peptides, and nucleic acids attract attention due to the similarity of these structures to the human body, their affinity for target organs, and their biological compatibility [[7], [8], [9]].

Dopamine, a physiological amine, is formed by removing carboxylic acid from the 3,4-dihydroxy-L-phenylalanine (L-DOPA) in the brain and kidney. Due to its adhesive properties, dopamine can be coated on an inorganic or organic surface by the oxidative polymerization under slightly alkaline conditions at the nanometer scale, making dopamine unique in terms of the bioinspired approach [10]. Although the formation of the polydopamine (PDOP) structure has not been fully elucidated, it is known that it is basically a structure obtained by oxidative self-polymerization of dopamine under alkaline conditions (pH 8.5). This polymer, secreted by oysters in the sea, is also used in many different areas, including the biomedical field, for applications such as protective coating, energy harvesting, tissue engineering, biosensing, bioimaging, molecular printing, wound dressing, and drug release and delivery [[11], [12], [13], [14], [15]]. This widespread use of the PDOP structure in the biomedical field can be attributed to the molecule's high biocompatibility, easy preparation, unique physicochemical properties, and versatile functionality. When considering this aspect, the bioadhesive properties of PDOP materials and their ability to easily reduce metals such as gold and silver to form plasmonic nanoparticles (NPs) make them suitable for advanced technological applications, such as controlled drug release [[16], [17], [18], [19]].

PDOP is a structure that has potential for use in drug release studies, both as a coating and as a nanoparticle [2,19]. Additionally, these structures have potential for use in phototherapy applications due to their strong NIR absorptions. It is worth noting that nanoparticle forms of metals such as Au, Pd, and Ag also exhibit photothermal properties due to their plasmonic properties, although the NIR-based approach involves NIR adsorption and photothermal conversion [20,21]. However, there have been few studies on the combined preparation and use of these two photothermal effect structures for phototherapy applications. In previous studies, plasmonic nanoparticles were either used as cores and coated with PDOP or mixed [[22], [23], [24], [25], [26], [27], [28]]. Therefore, it is necessary to evaluate a method in which structures such as PDOP and AuNP are prepared and applied in a combined manner. In this study, PDOP NPs were combined with plasmonic NPs, including Core-satellite-like architecture decorated AuNPs, for direct and laser-induced release (Scheme 1).

Unlike the studies in the literature, directly prepared AuNP@PDOP NPs were used instead of PDOP coating in this study for the plasmonic photothermal drug release approach. The particle sizes and morphologies of PDOP NPs synthesized in uniform NP sizes were characterized by techniques such as dynamic light scattering (DLS) and scanning electron microscopy (SEM). The structural properties of PDOP NPs and AuNPs decorated PDOP NPs were evaluated using fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD) methods. Drug-loaded PDOP NPs and AuNP@PDOP NPs were used in ON/OFF based drug release applications with 808 nm laser excitation. Laser power and the exposure time of the NIR were optimized. In order to determine the toxicity/anticancer effects caused by the drug-loaded particles and laser applications on the cells, cytotoxicity/biocompatibility studies were performed in both healthy (mouse fibroblast, L929) and cancer (human neuroblastoma, SHSY-5Y) cell lines. Considering the use of EPI due to the mechanism of action according to the genotoxicity properties of the particles, effects on reactive oxygen species (ROS) production and apoptotic properties were also examined. When the ease of application, thermal efficiency, drug release, and loading properties of the approach evaluated within the scope of the study are evaluated together, it is predicted that it may be very useful in terms of cancer therapy.