Toxicity-shielded Ag-Pt-ICG nanocomposite with photothermal-enhanced ionic release for lung cancer therapy

Background Silver nanoparticles (AgNPs) show antitumor potential but are limited by off-target oxidative toxicity. By integrating platinum nanoparticles (PtNPs) with indocyanine green (ICG)-mediated near-infrared (NIR) responsiveness, we developed an Ag-Pt-ICG (API) nanocomposite for fluorescence imaging and combined lung cancer therapy with enhanced therapeutic efficacy. Methods Ultrasmall Ag-Pt nanocomposites were synthesized via a seeded-growth strategy and subsequently functionalized with peptides to yield the intermediate conjugate AP-peptide (AP/PP). The photosensitizer indocyanine green bearing an NHS-ester group (ICG-NHS) was conjugated to the nanocomposites via peptide linkage, yielding API constructs. Comprehensive physicochemical characterization, including morphology, particle size, elemental composition, and colloidal stability, was conducted. We evaluated biosafety, and antitumor performance through a series of in vitro and in vivo assays. Results The API-based nanocomposites possessed typical nanoscale morphology and showed superior dispersion stability in serum-supplemented DMEM compared with PBS. Upon 808 nm NIR light irradiation, these nanocomposites achieved efficient photothermal conversion, excellent photothermal cycling stability, and NIR-triggered ROS production, endowing them with combined photothermal/photodynamic therapeutic effects. Under acidic conditions at pH 6.5, the nanocomposites could release silver ions into the surrounding medium, and 808 nm laser irradiation further accelerated silver ion release relative to the control group. In vitro results revealed that combined treatment with API nanocomposites and 808 nm NIR irradiation significantly suppressed the viability of A549 cells and elevated intracellular ROS levels. In vivo experiments confirmed that the combined treatment of API nanocomposites with 808 nm NIR laser exerted prominent tumor growth inhibition and alleviated tumor burden in tumor-xenografted mice compared with control groups. Forty-eight-hour in vivo fluorescence imaging confirmed the effective tumor accumulation of the nanocomposites. The fluorescence signal gradually decreased at later time points, suggesting time-dependent elimination while maintaining detectable tumor retention during the observation period. Furthermore, preliminary biosafety assessment confirmed no evident acute systemic toxicity under the tested conditions, which was evidenced by stable body weight changes, normal liver and renal function-related serum biochemical parameters, as well as hematoxylin-eosin staining results of major vital organs. Collectively, all these findings demonstrate that the as-prepared API nanocomposites are promising multifunctional nanoplatforms for NIR-activated combined tumor therapy with satisfactory biocompatibility. Conclusion The NIR-activated API hybrid nanoplatform synergizes photothermal-photodynamic therapy with Ag-induced cytotoxicity while suppressing off-target ROS toxicity via Pt-mediated antioxidant activity. This approach offers a clinically translatable strategy to enhance both the therapeutic efficacy and safety profile of metal-based nanotherapeutics. Download: Download high-res image (214KB) Download: Download full-size image