Biomimetic Atorvastatin Self-Assembled Nanomedicine Inhibits the Cyclooxygenase-2/Prostaglandin E2 Pathway Enhanced Photothermal and Antitumor Immunity.

Abstract

Cancer continues to pose remarkable medical challenges worldwide. While current cancer therapies can lead to initial clinical improvement, they are often followed by recurrence, metastasis, and drug resistance, underscoring the urgent need for innovative treatment strategies. Atorvastatin calcium (AC), a widely used lipid-lowering and anti-inflammation drug in the clinic, has shown antitumor potential. To further improve the antitumor efficacy, we developed self-assembled AC and polydopamine (PDA) nanoparticles whose surface was coated with macrophage membranes (CM) as a biomimetic drug delivery system [AC@PDA@CM (APM)]. APM showed high drug-loading capacity, excellent stability, excellent bioavailability, and tumor-targeting ability, ultimately achieving photothermal synergistic cancer immunotherapy. Our findings indicate that APM efficiently delivers AC to tumor sites while leveraging photothermal therapy (PTT) to enhance local tumor ablation and antitumor immune effect. Notably, APM mitigates tumor immunosuppression triggered by PTT through AC, suppressing the COX-2/PGE2 pathway and immune evasion signal CD47. Furthermore, APM notably reduced nonspecific distribution and side effects, which is conducive to ensuring the safety level of medication. This integrated approach boosts therapeutic efficacy and highlights the potential of APM as a multifunctional agent for cancer therapy, paving the way for future clinical applications.