Hyperthermia combined with nanoparticles to enhance cytotoxic effects of fresh human soft tissue sarcoma.

Abstract

e23570 Background: Sarcomas represent 1% of all adult cancers and 20% of all pediatric cancers worldwide.Sarcomas are heterogeneous with more than 50 histologic subtypes involving the mesenchyme including bones, muscle, fat, blood vessels, and nerves. Patients with high-risk localized or advanced disease are treated with the combination of neoadjuvant or adjuvant chemotherapy, radiation, and surgical resection have all failed to substantially improve overall survival (OS).4 Novel treatments are desperately needed in the management of soft tissue sarcoma. Thermal ablation of sarcoma may offer a novel method for eradicating the disease. Polymer based nanoparticles that can be stimulated with light to generate heat (photothermal nanoparticles) have been developed previously and used to induce. The goal of the current work is to utilize these nanoparticles for selected ablation of sarcoma. Methods: Polymer nanoparticles were first prepared in the in our lab through the synthesis of 2‐ethylhexyl cyclopentadithiophene 2,1,3‐benzoselenadiazole (PCPDTBSe). Nanoparticles of this polymer were prepared using an oil-water emulsion technique, with FITC labeled polyethylene glycol as the stabilizing agent, to create an aqueous suspension. The nanoparticles were characterized for their size and ability to generate heat when stimulated with 800 nm laser light (180J/cm2). Fresh Soft tissue sarcoma samples are obtained through informed consent and approval of the institutional IRB. Nanoparticles were injected into sarcoma in a volume of 100ul, at a concentration of 250ug/ml. The tissues were then exposed to the laser source to generate heat. Controls included the injection of the sarcoma with the nanoparticles and no laser exposure, as well as the injection of water, plus laser exposure. Results: Sarcomas vary in their ability to take up and response to nanoparticles. We have found that liposarcoma samples are extremely leaky and do not hold the injection of nanoparticles, which leach out of the tumor. Conclusions: Future directions include studies that would involve targeted, immunotherapy and chemotherapy given with nanoparticles that facilitate combinatory and unique individual cytotoxic effects of the soft tissue sarcoma subtypes.