Abstract 4430: Enhanced thermal ablation for the treatment of triple negative cancer
Authors: Shen Haifa , Ferrari Mauro 
Published: June 2012

Abstract
Triple negative breast cancer (TNBC) cells are ER-and PR-negative, and lack overexpression of HER2. This type of cancer accounts for 12-20% of all breast cancer cases. Although TNBC tumors do respond to conventional chemotherapy, their relapse rate remains high. The overall poor prognosis of patients with TNBC and the tendency to relapse demand for new therapeutic options. In this study, we explored tissue-specific thermal ablation for the treatment of this deadly disease with a newly developed multistage vector (MSV) delivery system.
The MSVs are biocompatible and biodegradable mesoporous silicon particles. They offer tissue-specific delivery of nano-formulated therapeutic agents for personalized treatment of human diseases. MSVs loaded with nano-formulated drugs travel to tumor vasculature, where the nanoparticles get released from the MSV carrier, and enter the tumor tissue for drug action. We have recently demonstrated that multistage delivery of liposomal-EphA2 siRNA provided sustained gene silencing, and inhibited ovarian tumor growth in mouse orthotopic tumor models after a single injection of siRNA-loaded MSVs (Cancer Res. 70: 3687-96, 2010). In the current study, we tested the delivery of hollow gold nanoparticles (HAuNP) with MSV for thermal ablation treatment of TNBC. We measured tumor accumulation of various MSVs with variable parameters including size, shape, and surface chemical modifications in mouse models of human breast cancers. The 1,000 nm × 400 nm discoidal MSVs had the highest tumor accumulation rate over the larger discoidal particles and those of hemispherical shape, with up to 10% of total injected particles in the tumor tissue. HAuNPs with an average diameter of 30 nm could be efficiently loaded into the pores of MSVs. We used near infrared (NIR) to trigger heat generation of the HAuNPs. Surprisingly, the HAuNP-loaded MSVs generated twice as much heat as the same amount of free HAuNPs in solution. This was most likely due to the confinement of the small HAuNPs in the pores of the mesoporous silicon particles. Detailed mechanism is under investigation. In cell culture, MSVs were efficiently taken up by human breast cancer cells. Mice bearing MDA-MB-231 tumors were injected with free HAuNPs or HAuNP-loaded MSVs, and tumors were treated with a NIR laser beam for three rounds. The HAuNP-loaded MSVs were superior to free gold nanoparticles in triggering tumor necrosis. In contrast to most chemotherapy drugs that killed cancer cells more efficiently than tumor initiating cells, we observed a significant drop in the percentage of tumor initiating cells.
The strategy discussed here represents a radical change to breast cancer treatment. HAuNP-loaded MSVs can be an effective agent to treat TNBC by thermal ablation. It is highly possible this treatment would result in less chance of relapse due to the preferential killing of tumor initiating cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4430. doi:10.1158/1538-7445.AM2011-4430