Combined chemotherapy and photothermal therapy (PTT) represents a promising approach for enhancing cancer treatment efficacy. This study aimed to develop arsenic trioxide (ATO) and poly(cyclopentadithiophene-alt-benzothiadiazole) (PCPDTBT)-loaded nanoparticles (ATO/PCPDTBT@NPs) to evaluate their synergistic efficacy in inhibiting lung cancer growth and metastasis.

Nanovesicles were synthesized via a streamlined protocol and subjected to 808 nm NIR irradiation to assess their photothermal conversion capabilities. The therapeutic efficacy was evaluated in vitro using A549 lung carcinoma cells to assess apoptosis, invasion, and migration, and in vivo to monitor tumor volume reduction.

The nanoparticles exhibited excellent hemocompatibility and low cytotoxicity while demonstrating robust photothermal conversion, inducing a rapid 20.8°C temperature rise within five minutes. In vitro, ATO enhanced apoptotic pathways and suppressed metastasis, while the combination therapy significantly reduced cell viability (OD: 0.23 vs. 0.62 in controls) and migration (13.6% vs. 74.9%), outperforming monotherapies. In vivo, the chemo-photothermal treatment reduced tumor volumes by 2.5- and 3-fold compared to ATO or PTT alone, confirming superior antitumor effects.

These findings highlight the dual-action ATO/PCPDTBT@NPs nanoplatform as a potential multifaceted strategy for effective tumor suppression and metastasis inhibition.