PEGylated heptamethine cyanine nanoparticles improve photothermal efficacy and elicit durable anti-tumour immunity in breast cancer mouse model.

Photothermal therapy (PTT) induces immunogenic tumour cell death and stimulates both innate and adaptive immunity. In our previous study, we showed promising in vitro and in ovo anti-tumour efficacies of a quinoline-modified heptamethine cyanine (QuCy7) encapsulated with polyethylene glycol (PEG), forming QuCy7@mPEG NPs. This study evaluated its anti-tumour efficacy and immunomodulatory effects in a syngeneic breast cancer mouse model. QuCy7@mPEG NPs induced stronger hyperthermic effect (~45 °C) compared to QuCy7 alone (~40 °C), significantly delayed tumour growth (84.9%) and achieved 50% tumour elimination. Cytokine analysis showed elevated levels of IL-6, TNF-α, IFN-γ and IL-17A, along with reduced TGF-β expression. Post-treatment, increased infiltration of neutrophils, IL-6-producing M1-like macrophages, T-helper 1, and cytotoxic T cells was observed. Notably, QuCy7@mPEG NPs enhanced long-term tumour-specific immunity, evidenced by rapid CD4+ effector memory T cells activation upon tumour re-challenge. These findings highlight the potential of QuCy7@mPEG NPs as an immune-stimulatory photothermal agent for cancer treatment.