Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core???shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Automated summary

Photothermal therapy combined with immunotherapy has shown promising potential in treating cancer. In this study, silica-based core-shell nanoparticles were engineered to deliver a photothermal agent and a BRD4 inhibitor for tumor elimination. The surface roughness of the nanoparticles was increased to enhance internalization and improve the therapeutic effect. Animal studies demonstrated that these multifunctional nanoparticles effectively eradicated melanoma, activated tumor-specific immune responses, and prevented metastasis and recurrence. This innovative approach holds great promise for combined cancer therapy.