Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2021-01-01
|
| Series: | Nanoscale Research Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11671-020-03459-x |
| _version_ | 1797722988936691712 |
|---|---|
| author | Patrick McKernan Needa A. Virani Gabriela N. F. Faria Clément G. Karch Ricardo Prada Silvy Daniel E. Resasco Linda F. Thompson Roger G. Harrison |
| author_facet | Patrick McKernan Needa A. Virani Gabriela N. F. Faria Clément G. Karch Ricardo Prada Silvy Daniel E. Resasco Linda F. Thompson Roger G. Harrison |
| author_sort | Patrick McKernan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T09:56:44Z |
| format | Article |
| id | doaj.art-b977638808f64fcea32955f1aef0df5c |
| institution | Directory Open Access Journal |
| issn | 1556-276X |
| language | English |
| last_indexed | 2024-03-12T09:56:44Z |
| publishDate | 2021-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nanoscale Research Letters |
| spelling | doaj.art-b977638808f64fcea32955f1aef0df5c2023-09-02T12:11:45ZengSpringerOpenNanoscale Research Letters1556-276X2021-01-011611910.1186/s11671-020-03459-xTargeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast CancerPatrick McKernan0Needa A. Virani1Gabriela N. F. Faria2Clément G. Karch3Ricardo Prada Silvy4Daniel E. Resasco5Linda F. Thompson6Roger G. Harrison7Department of Neurology, Neurosurgery, and Radiation Oncology, University of Oklahoma Health Sciences CenterDepartment of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School, and Dana-Farber Cancer InstituteSchool of Chemical, Biological and Materials Engineering, University of OklahomaSchool of Biomedical Engineering, University of OklahomaSchool of Chemical, Biological and Materials Engineering, University of OklahomaSchool of Chemical, Biological and Materials Engineering, University of OklahomaArthritis and Clinical Immunology Program, Oklahoma Medical Research FoundationSchool of Chemical, Biological and Materials Engineering, University of OklahomaAbstract 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.https://doi.org/10.1186/s11671-020-03459-xSingle-walled carbon nanotubesPhotothermal therapyAnnexin A5Breast cancerImmune checkpoint inhibitor |
| spellingShingle | Patrick McKernan Needa A. Virani Gabriela N. F. Faria Clément G. Karch Ricardo Prada Silvy Daniel E. Resasco Linda F. Thompson Roger G. Harrison Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer Nanoscale Research Letters Single-walled carbon nanotubes Photothermal therapy Annexin A5 Breast cancer Immune checkpoint inhibitor |
| title | Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer |
| title_full | Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer |
| title_fullStr | Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer |
| title_full_unstemmed | Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer |
| title_short | Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer |
| title_sort | targeted single walled carbon nanotubes for photothermal therapy combined with immune checkpoint inhibition for the treatment of metastatic breast cancer |
| topic | Single-walled carbon nanotubes Photothermal therapy Annexin A5 Breast cancer Immune checkpoint inhibitor |
| url | https://doi.org/10.1186/s11671-020-03459-x |
| work_keys_str_mv | AT patrickmckernan targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT needaavirani targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT gabrielanffaria targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT clementgkarch targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT ricardopradasilvy targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT danieleresasco targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT lindafthompson targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer AT rogergharrison targetedsinglewalledcarbonnanotubesforphotothermaltherapycombinedwithimmunecheckpointinhibitionforthetreatmentofmetastaticbreastcancer |