Ablation of Venous Malformations by Photothermal Therapy with Intravenous Gold Nanoshells
*Claire A. Ostertag-Hill1, *Kathleen Cullion2, *Michelle Pan2, *Brian P. Timko3, *Elisa Boscolo4, *Daniel S. Kohane5
1. Surgery, Boston Children's Hospital, Boston, MA, United States. 2. Medical Critical Care, Boston Children's Hospital, Boston, MA, United States. 3. Biomedical Engineering, Tufts University, Medford, MA, United States. 4. Experiment Hematology and Cancer Biology, Cincinnati Children's Hospital, Cincinnati, OH, United States. 5. Anesthesiology, Critical Care, and Pain Management, Boston Children's Hospital, Boston, MA, United States.
Introduction:
Venous malformations (VMs) cause significant disfigurement, pain, and complications such as bleeding and coagulopathy. Current treatment for patients with VMs entails life-long pharmacotherapy or surgical procedures that have limited efficacy. Here, we explored whether intravenously administered nanoparticle-based agents could be used to destroy VMs by photothermal therapy, using gold nanoshells (AuNS) that generated heat following irradiation with near-infrared (NIR) light.
Study Design:
AuNS were synthesized by galvanically reducing gold at the surface of cobalt seeds and were characterized. Using the HUVEC-TIE2-L914F murine model of VMs, we assessed nanoparticle accumulation within the VM and biologic effects of photothermal therapy. Irradiation was performed using an 808nm NIR iodine laser.
Results:
Following intravenous administration of AuNS to mice with VMs, 7.1±9.6 ng elemental gold/mg of tissue was detected in VMs. VM size in response to four treatment protocols was examined: normal saline without NIR irradiation (SAL), normal saline with NIR irradiation (SAL+NIR), AuNS without NIR irradiation (AuNS), and AuNS with NIR irradiation (AuNS+NIR). In animals injected with SAL, VM size increased 3-fold over 3 weeks (from 300 to 900mm3), whether or not they were irradiated. In the AuNS group (Fig. 1), VM size increased 2.2-fold (from 300 to 700mm3). In contrast, in the AuNS+NIR group (Fig. 1), VMs began regressing 48h after irradiation and reduced in size greater than 17-fold, from 300mm3 to a mean of 17.5±18.8mm3, including two VMs that were completely eliminated. This was a significant decrease in size compared to SAL, SAL+NIR, and AuNS groups (p<0.0004 or lower). While photothermal therapy significantly reduced or eliminated VMs, skin burns did occur. There was no evidence of organ injury or inflammation by laboratory data or histology.
Conclusions:
This is the first demonstration of accumulation of intravenously administered nanoparticles in VMs and of intravenously administered nanoparticles used to destroy VMs by photothermal therapy.
Back to 2024 Posters