Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Developing a Noninvasive High-efficacy Technique for the Treatment of Infantile Hemangioma using a Nanoparticle-Conjugated Delivery System
Hakan Orbay, MD, PhD, Lindsey Harrison, BS, Kamaljit Devi, BS, Yuanpei Li, PhD, Wenwu Xiao, PhD, Kit Lam, MD, PhD, David E. Sahar, MD.
UCDavis, Sacramento, CA, USA.

PURPOSE:Infantile hemangiomas (IHs) are benign, vascular tumors of childhood affecting 5-10% of all infants. Surgical treatment of IHs is difficult because of the highly vascular nature of the tumor and the current non-surgical treatment modalities are far from curing the disease. The purpose of this study is to define a noninvasive, high-efficacy treatment method for IHs by first establishing a reproducible mouse model of IH and treating the animals with a combination of photodynamic therapy and pharmacotherapy delivered by a nanoparticle carrier.
METHODS:Twenty, 5-week-old, male nude mice were used for the study. 1.5 x 106 mouse hemangioendothelioma cells (ATCC® CRL-2587™, Manassas, VA) were injected subcutaneously to bilateral axillary regions of mice. Tumor size was measured periodically with digital caliper and tumor volume was calculated. When the tumors reached a diameter of 0.5 cm in vivo imaging was performed. For the in vivo imaging, the animals were injected with 200 µl of nanoporphyrin nanoparticle conjugated with a fluorophore (DiD) via the tail vein. Images were obtained using a near-infrared imaging station 3, 6, and 24 hours after the injection. The animals were euthanized after the in vivo imaging and major organs and IHs were harvested for ex vivo imaging. The IHs were further examined histologically with von Willebrand Factor (vWF) immunofluorescence staining and Hematoxylene and Eosin (HE) staining.
RESULTS:Mice started to grow tumors approximately 1 week after injection. Tumors exhibited a rapid growth rate especially 19 days after injection resembling the rapid growth phase of IHs in humans. In vivo imaging revealed that the nanoporphyrin nanoparticles reached maximum concentration in the IHs 24 hours after the injection (Fig.1). Ex vivo imaging showed that the majority of the injected dose was accumulated in the liver as expected (Fig.1). Macroscopically the IHs were mainly composed of large vascular channels filled with blood. vWF immunofluorescence staining and HE staining confirmed that the tumors had the characteristic highly vascular structure of IHs.
CONCLUSION:The model we have created mirrors the characteristic of natural IH, making it a good model to test the therapy proposed here. The next step in the study will be the treatment of the tumors with a combination of photodynamic therapy and propranolol loaded nanoporphyrin nanoparticles. Photodynamic therapy will destroy the vascular cells of IH by triggering the formation of toxic reactive oxygen species. In addition near-infrared laser will stimulate the nanoparticles to release propranolol at the lesion site producing a double therapeutic effect.


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