Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer

• DOI: 10.1186/s11671-020-03459-x
• Publication Date: 2021-01-07T13:04:57Z
• Authors: Patrick McKernan; Needa A. Virani; Gabriela N. F. Faria; Clément G. Karch; Ricardo Prada Silvy; Daniel E. Resasco; Linda F. Thompson; Roger G. Harrison
• Keywords: 03 medical and health sciences; Breast cancer; 0302 clinical medicine; Nano Express; TA401-492; Single-walled carbon nanotubes; Immune checkpoint inhibitor; Annexin A5; Photothermal therapy; Materials of engineering and construction. Mechanics of materials; 3. Good health

AbstractThe greatest contributors to cancer mortality are metastasis and the consequences of its treatment. Here, we present a novel treatment of metastatic breast cancer that combines photothermal therapy with targeted single-walled carbon nanotubes (SWCNTs) and immunostimulation with a checkpoint inhibitor. We find that the selective near-infrared photothermal ablation of primary orthotopic EMT6 breast tumors in syngeneic BALB/cJ mice using an annexin A5 (ANXA5) functionalized SWCNT bioconjugate synergistically enhances an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4)-dependent abscopal response, resulting in an increased survival (55%) at 100 days after tumor inoculation. In comparison, there was no survival at 100 days for either photothermal therapy by itself or immunostimulation by itself. Prior to photothermal therapy, the SWCNT-ANXA5 bioconjugate was administered systemically at a relatively low dose of 1.2 mg/kg, where it then accumulated in tumor vasculature via ANXA5-dependent binding. During photothermal therapy, the average maximum temperature in the tumor reached 54 °C (duration 175 s). The mechanism of prolonged survival resulting from combinatorial photothermal ablation and immune stimulation was evaluated by flow cytometric quantification of splenic antitumoral immune effector cells and serum cytokine quantification.