MP57-14 TOXICITY AND BIODISTRIBUTION OF GOLD NANOPARTICLE-BASED PHOTO-IMMUNO-NANOTHERAPY FOR BLADDER CANCER (2019)

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (MP57)1 Apr 2019MP57-14 TOXICITY AND BIODISTRIBUTION OF GOLD NANOPARTICLE-BASED PHOTO-IMMUNO-NANOTHERAPY FOR BLADDER CANCER Gregory Barton*, Yang Liu, Paolo Maccarini, Gregory Palmer, Wiguins Etienne, Wei Phin Tan, Tuan Vo-Dinh, and Brant Inman Gregory Barton*Gregory Barton* More articles by this author , Yang LiuYang Liu More articles by this author , Paolo MaccariniPaolo Maccarini More articles by this author , Gregory PalmerGregory Palmer More articles by this author , Wiguins EtienneWiguins Etienne More articles by this author , Wei Phin TanWei Phin Tan More articles by this author , Tuan Vo-DinhTuan Vo-Dinh More articles by this author , and Brant InmanBrant Inman More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556622.09729.2aAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: We developed a novel treatment for bladder cancer (BC): a combination of gold nanoparticle-based immune- and photothermal therapy called SYMPHONY, which ablates primary tumors, induces potent anti-tumor immunity, and abscopally destroys distant metastases. Here we analyzed toxicity and biodistribution of SYMPHONY gold nanostars in murine BC models. METHODS: MB49 syngeneic bladder tumors were grown in C57BL/6 mice to 100 mm2. Tumors were treated with SYMPHONY and tissues obtained from lung, liver, brain, spleen, kidney, heart, and intestine at selected timepoints from minutes to months post-therapy. Gold nanostars (GNS) were given via tail vein injection, dosed at 20mg/kg or 80 mg/kg. We assessed toxicity multiply. First, with histopathology on necropsied tissue to assess for organ injury. Second, blood chemistries and body weight were measured longitudinally. Third, F4/80 immunohistochemistry staining for macrophages was done in spleen and liver. Fourth, tissues were digested with aqua regia for inductively coupled plasma mass spectrometry (ICP-MS) to quantify gold mass within organ sites. GNS uptake was calculated as % injection dose (ID)/g tissue. Last, we labeled GNS with I-124, injected via tail vein at 20mg/kg and obtained positron emission tomography (PET) images at 0h, 4h, 24h, 48h, and 120h with an animal microPET scanner. RESULTS: H&E examination showed healthy and intact tissue. There was no significant difference between control and GNS-treated animals on pathology, nor in blood chemistry results, and no evidence of biochemical toxicity. F4/80 IHC staining showed GNS within macrophages but no inflammatory response triggered by the GNS. GNS uptake (%ID/g) was highest in the spleen (median 105%), then liver (40%), with remaining organs <20%. No brain uptake was noted. I-124 labeled GNS PET imaging showed that GNS travelled to the liver and spleen after 24 hours, and that free I-124 leached into the thyroid (Figure). CONCLUSIONS: SYMPHONY treatment using gold nanostars shows no evidence of significant toxicity in BC models; this therapy should be safe to translate to humans. Biodistribution studies show gold metabolism with the splenic and hepatic reticuloendothelial system as the primary method of disposal. SYMPHONY provides local and distant BC control and is an exciting new therapy for BC. Source of Funding: DOD grant WXWH-17-1-0567 Durham, NC© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e818-e818 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gregory Barton* More articles by this author Yang Liu More articles by this author Paolo Maccarini More articles by this author Gregory Palmer More articles by this author Wiguins Etienne More articles by this author Wei Phin Tan More articles by this author Tuan Vo-Dinh More articles by this author Brant Inman More articles by this author Expand All Advertisement PDF downloadLoading ...