Abstract 2891: Photodynamic therapy using PMB polymer as a new nanotransporter of verteporfin for the treatment of lymph node metastasis in breast cancer

Abstract

Abstract [Introduction] Although axillary lymph node dissection (ALND) has been part of breast cancer surgery, the impact of ALND on survival of breast cancer is still to be elucidated. At the same time ALND is associated with several complications such as lymphedema, seroma formation and shoulder dysfunction. Therefore, the development of minimally invasive procedure alternative to ALND is necessary. Photodynamic therapy (PDT) is a noninvasive optical therapeutic method in which the topical or systemic delivery of photosensitizer is followed by irradiation with broadband red light. Despite advantages such as longer wave length and a short photosensitivity period, verteporfin, a hydrophobic photosensitizer, has not yet been applied in cancer treatment. Previously, we have reported that PMB polymer forms a stable aggregate in water that can enhance the solubility of verteporfin, and PDT using a PMB-verteporfin complex is a promising anticancer therapy (Cancer Biotherapy and Radiopharmaceuticals 2011, Epub ahead of print). In this study, the efficacy of PDT using PMB polymer as a new nanotransporter of verteporfin for the treatment of lymph node metastasis was evaluated.[Materials and Methods]To develop a murine lymph node metastasis model, 5x105 human epithelial carcinoma A431 cells with stable expression of GFP were injected to the forearm of BALB/c nude mice. PMB polymer and verteporfin were mixed at the ratio of 25:1, and sonicated to make the PMB-verteporfin aggregate. Seven days after inoculation of cancer cells, PMB-verteporfin aggregate or PMB polymer alone was injected to the forearm of BALB/c nude mice. The concentation of verteporfin in lymph node was determined by measuring the fluorescence emitted at 700 nm (with excitation at 430 nm) using a microplate reader (BioTek, Vermont, USA). One hour after injection of aggregate or PMB alone, 75 J of light energy was delivered using a 640 nm diode laser for a total treatment time of 1 minute. Mice were randomly assigned to the combination of PMB-verteporfin inpjection and light exposure, light exposure alone, PMB-verteporfin injection alone, and PMB injection alone. Ten days after PDT, lymph nodes were harvested to evaluate metastasis by stereoscopic fluorescence microscope. [Results] Concentration of verteporfin was 23.9µg/g tissue in brachial and 9.5µg/g tissue in axillary lymph node. Lymph node metastasis rates of combination of PMB-verteporfin injection and light exposure group, light exposure group, PMB-verteporfin injection group, and PMB injection group were 12.5%, 57.1%, 33.3% and 56.3%, respectively. [Conclusion] These data suggested that PDT using PMB polymer as a new nanotransporter of verteporfin could be a minimally invasive treatment of lymph node metastasis in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2891. doi:1538-7445.AM2012-2891