Novel targeted annexin V–nanoparticle conjugate for cancer photophermal therapy

Abstract

Triple negative breast cancer represents a strong clinical challenge due to its high invasiveness and the lack of therapeutic targets. To overcome this problem, recent combination therapeutic strategies have been implemented. When treated during early phases, a combination of surgery, chemotherapy, and irradiation therapy is usually performed, which significantly improves the overall survival of the patients. However, when detected later, triple negative breast cancer begins to metastasize, considerably reducing the effectiveness of the treatments. As a potential solution to this problem, we propose a novel treatment of metastatic triple negative breast cancer that combines targeted photothermal therapy with a checkpoint inhibitor treatment. Photothermal therapy is a recent irradiation therapy based on the electromagnetic radiation of photosensitizers. When exposed to specific electromagnetic radiation, photosensitizers absorb irradiating energy and releases it as heat to the surrounding environment. The resulting heat can be used to disrupt the membranes of cancer cells or to denature essential cytoplasmic proteins, inducing tumor elimination. This approach is interesting because it can induce the release of tumor antigens and proinflammatory cytokines that can be used to treat metastases. The effectiveness of a novel targeted conjugate for targeted photothermal therapy based on single-walled carbon nanoparticles was assessed in vitro, and the ability of the treatment to release proinflammatory cytokines in mice was demonstrated. This new treatment showed significant cytotoxicity against EMT6 triple negative breast cancer cells, while not affecting the cell viability of a healthy endothelial cell model in vitro. In a mouse model, the treatment has shown to be effective in releasing cytokines TNFα, IFNγ and IL-6 into the bloodstream of the mice. By combination with the checkpoint inhibitor anti-CTLA-4, this approach has shown promising results in the treatment of triple negative breast cancer metastases in mice.