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

Nanoscale Research Letters

Linda F. Thompson¹  Patrick McKernan²  Needa A. Virani³  Clément G. Karch⁴  Gabriela N. F. Faria⁵  Daniel E. Resasco⁵  Ricardo Prada Silvy⁵  Roger G. Harrison⁵ 

[1] Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation;Department of Neurology, Neurosurgery, and Radiation Oncology, University of Oklahoma Health Sciences Center;Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School, and Dana-Farber Cancer Institute;School of Biomedical Engineering, University of Oklahoma;School of Chemical, Biological and Materials Engineering, University of Oklahoma;

关键词: Single-walled carbon nanotubes;    Photothermal therapy;    Annexin A5;    Breast cancer;    Immune checkpoint inhibitor;   

DOI  :  10.1186/s11671-020-03459-x

来源: DOAJ

【 摘 要 】

Abstract The 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.

【 授权许可】

Unknown