Assessment of Apoptosis-like Cell Death in A549 Lung Cancer Cells Induced by Photoactivated Gold Shell-Isolated Nanostars

Abstract Lung cancer remains one of the most lethal malignancies worldwide, with survival rates dropping sharply at advanced stages. Conventional therapies are limited by systemic toxicity and poor selectivity, motivating the development of alternative strategies such as photothermal therapy (PTT). Herein, we investigate gold shell-isolated nanostars (AuNS@SiO2) as photothermal agents for near-infrared (NIR)-triggered cancer treatment in A549 lung cancer cells. The silica shell enhances colloidal stability and protects the plasmonic core, while the nanostar morphology enables efficient NIR light-to-heat conversion. In addition to the photothermal response, AuNS@SiO2 generated singlet oxygen (1O2) under NIR irradiation and was associated with irradiation-dependent changes in the intracellular ROS-related fluorescence, indicating a complementary photochemical oxidative contribution to the photoinduced cellular response. AuNS@SiO2 exhibited minimal cytotoxicity in A549 cells in the absence of irradiation, but induced a concentration-dependent decrease in viability upon NIR photoactivation. Apoptosis/necrosis assays revealed a shift from viable cells toward populations exhibiting early and late apoptosis-associated features, with minimal necrosis-associated events. Taken together, these findings indicate that the biological response induced by NIR-photoactivated AuNS@SiO2 involves efficient photothermal heating together with a complementary oxidative photochemical contribution and is predominantly associated with apoptosis-like cell death, supporting their potential as effective agents for NIR-based lung cancer therapy.