A Synergistic 3D-Printed Collar Transforms Radiofrequency Ablation Into Potent Thermal Immunotherapy for Lung Cancer

Interventional thermal therapy, such as radiofrequency ablation (RFA), is a preferred therapy for non-small cell lung cancer (NSCLC) patients. However, part of some patients will still suffer from tumor recurrence due to incomplete ablation (e.g., restricted thermal conductivity, etc.). Notably, RFA can evoke anti-tumor immunity by releasing tumor-associated antigens (TAAs), but this effect is weak. Herein, to boost thermal and immune therapeutic efficiency for complete tumor eradication, an effective nano-adjuvant (CpG-pIL12-LDHs, LC12), layered double hydroxides (LDHs) carrying immune stimulators, CpG ODN (CpG) and IL-12 plasmid (pIL-12), is developed, which is further integrated into a 3D-printed collar for eliciting potent thermotherapy and therapeutic vaccine against lung cancer. The as-prepared 3D-printed adjuvant collar (3D-LC12) can be attached to the RFA electronic needle and respond to the radiofrequency electrical field during treatment, enhancing ablation temperature, area, and nano-adjuvant's diffusion. After release from the temperature-sensitive collar, LC12 can form an in situ therapeutic cancer vaccine, activate APCs, and remodel the tumor microenvironment (TME), triggering a robust antitumor immune response. Therefore, the current study demonstrates a multi-functional 3D-printed adjuvant collar for efficient eradication of lung cancer via one-time RFA-integrated therapy, providing a novel combined strategy for interventional thermal therapy against tumors.