Elimination of tumors and their metastasis by a thermally responsive silica nanoparticle decorated with an anti-PD-L1 antibody fragment.

Metastasis and recurrence remain the leading causes of cancer-related mortality; however, existing therapies offer limited protection against systemic tumor spread following primary treatment. Here, we report a dual-function nanoplatform, anti-programmed cell death protein-ligand 1 PD-L1 antigen-binding fragment (Fab)-conjugated thermally responsive silica (α-TRS) nanoparticles, rationally designed to achieve complete ablation of primary tumors through photothermal therapy (PTT) while simultaneously priming systemic antitumor immunity to suppress distant metastasis. Indocyanine green (ICG) was encapsulated within mesoporous silica nanoparticles with high efficiency (91.2%), and the Fab of an anti-PD-L1 antibody was site-specifically conjugated to the nanoparticle surface via NTA-Ni²⁺/His-tag chemistry. With 808 nm near-infrared (NIR) laser irradiation, α-TRS generated sufficient heat (∼50 °C) to induce ablative tumor cell death in vitro and achieved complete remission of 4T1 breast tumors and CT-26 colon tumors in vivo following intratumoral injection. Critically, mice cured of primary tumors by α-TRS-mediated PTT were fully protected against subsequent intravenous rechallenge with lung-metastatic 4T1 and CT-26 cells, whereas mice treated with PTT alone (TRS without Fab) showed only partial protection. This abscopal-like protection was mechanistically linked to the robust activation of tumor antigen-specific CD4⁺ and CD8⁺ T cells, including enhanced production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, perforin, and granzyme B in response to tumor antigens. These findings suggest that ablative PTT combined with local PD-L1 checkpoint blockade can convert a localized thermal intervention into durable systemic immunity, offering a promising proof-of-concept strategy for simultaneously treating primary tumors and preventing metastatic recurrence.