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

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.

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

“…The PTT‐induced “abscopal effect” is still too weak to suppress the growth of the remaining tumor margin. The combination of PTT with immunomodulation has been reported to demonstrate potential in cancer therapy 16, 17, 18, 19, 20. Furthermore, the tumor margin beyond effective PTT undergoes mild heating.…”

Black‐Phosphorus‐Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer

“…Compared to other conventional therapeutic techniques, PTT boasts many merits such as the simplicity, minimal invasiveness, low incidence of complications, as well as the high spatial and temporal precision of NIR light 8, 9, 10, 11. Various types of nanoagents have been explored to attain better PTT performance12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and in the treatment, intravenous injection of the nanoagents (to mice, for example) is followed by high‐power NIR laser irradiation for ablation 25, 26, 27, 28, 29. Despite recent progress, clinical adoption of PTT still faces several hurdles.…”

Improving Vaccine and Immunotherapy Design Using Biomaterials

“…Photothermal therapy works through local absorption of energy from a laser by nanoparticles draining into a tumor to generate local heating. Importantly, encapsulating TLRa in the NPs with a photothermal agent enhanced the tumor specific immune response and generated functional effector memory that protected against tumor rechallenge [72]. …”