Enhanced Gold Nanoparticle aggregation with cancer cell DNA for improved radiation therapy and immune response in cancer treatment

Abstract

In the United States, cancer is the second leading cause of death after heart disease and hundreds of thousands of people pass away each year due to this deadly disease. Many treatments for cancer are nonselective and do not provide long‐lasting immunity in case of recurrence. Gold nanoparticles can provide a more targeted radiation therapy and better effectiveness through heat generation and formation of reactive oxygen species via hydrolysis reaction which can cause DNA damage in the tumor. Unfortunately, gold particles have low photothermal transduction efficiency and must be aggregated to improve performance. To achieve this, positively charged gold nanoparticles were aggregated with MDA MB 231 cancer cell DNA to increase gold nanoparticle aggregation, to elicit higher photothermal efficiency, and to stimulate an immune response. In vitro analysis demonstrated DNA size and concentration dependent gold nanoparticle aggregation, which varied little in the pH range of 5.5 to 8.6. Furthermore, these aggregates elicited an immune response via delivery of DNA for direct transfection of antigen presenting cells. Tumor necrosis factor alpha released from mouse RAW macrophages increased in the presence of the cancer cell DNA aggregated gold particles. This work suggests that the promise of combination therapy using cancer cell DNA not only can improve photothermal therapy of gold nanoparticles, but also can elicit an immune response in cancer treatment.