Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

TLDR

The study develops a therapeutic strategy that combines adjuvant nanoparticle‑based photothermal therapy with checkpoint‑blockade immunotherapy to eliminate primary tumors, inhibit metastases, and prevent relapses. The authors encapsulate indocyanine green and the TLR‑7 agonist imiquimod in PLGA nanoparticles, enabling near‑infrared laser‑triggered photothermal ablation that releases tumor antigens and, together with anti‑CTLA4 blockade, stimulates vaccine‑like immune responses. In mouse models, this approach eradicates primary tumors, suppresses metastasis, and induces durable immunological memory that protects against tumor rechallenge.

Abstract

Abstract A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.