摘要Photothermal therapy(PTT)is a non-invasive and highly selective tumor treatment.However,it triggers an inflammatory re-action and other adverse effects,including damage to the surrounding healthy tissue and an increased risk of tumor prolifera-tion and metastasis.The cyclooxygenase-2(COX-2)/prostaglandin E2(PGE2)pathway plays a crucial role in regulating tumor development.In this study,we revealed that PTT activates the COX-2/PGE2 pathway.To mitigate the PTT-induced inflammation,based on polydopamine(PDA)and HS-β-cyclodextrin(HS-β-CD),we constructed a photothermal/anti-inflammatory nanoparticle system(named ICG@PDA-β-CD/CEL)loaded with the anti-inflammatory drug celecoxib(CEL)and the photosensitizer indocyanine green(ICG),which targets COX-2.This system helps PTT by(1)reducing pro-inflammatory molecules such as PGE2,tumor necrosis factor-α,and interleukin-6 and inhibiting the COX-2 and nuclear fac-tor kappa-B signaling pathways,(2)suppressing vascular endothelial growth factor production to inhibit tumor angiogenesis,and(3)preventing tumor cell migration and invasion.Further results indicated that ICG@PDA-β-CD/CEL significantly cur-tailed tumor cell invasion and migration in vitro and suppressed the COX-2/PGE2 pathway in vivo,thereby markedly inhibit-ing both orthotopic tumor growth and metastasis.ICG@PDA-β-CD/CEL exhibits potent antitumor effects through its com-bined anti-inflammatory and photothermal therapies,providing a promising strategy for alleviating PTT-related adverse effects.