ATP-responsive and functionalized framework nucleic acid for synergistic radio-immunotherapy

Traditional radiotherapy is ineffective against some aggressive and recurrent tumors. In clinical therapy, low-dose radiations are frequently utilized to lessen the negative effects of X-rays. There is an urgent need to develop a novel therapeutic strategy for adjuvant radiotherapy. An ATP-responsive and functionalized framework nucleic acid delivery system (Op-TGA) was developed using local irradiation, which can cause enormous ATP release from tumors. The framework nucleic acid carrying the nucleic acid fragment of immune adjuvant and antigen peptides can be massively aggregated and successfully released in a high-concentration ATP environment using this delivery platform. Thus, intravenous injection of Op-TGA into tumor-bearing mice after radiation can precisely concentrate around the tumor tissue, and once released, it is rapidly taken up by antigen-presenting cells, stimulating the cellular immune response. The conjunction of radiotherapy and Op-TGA has a significant synergistic anticancer efficacy and establishes an immunological memory effect to prevent tumor recurrence. Op-TGA developed here offers a new technique for Radio-immunotherapy that is closely related to clinical therapy and has great clinical application potential.