Liver metastasis is a common occurrence during the course of gastrointestinal disease. It has been found in 30-70% of patients who are dying of various malignancies including colorectal, breast, lung, and pancreas cancer. Surgery is a common therapy for liver metastasis;however, 5-year survival rates range from 25-40%, indicating the need to develop novel therapies. A part of developing novel therapies is the necessity to understand the development of liver metastasis. Kupffer cells (KC), the phagocytic cells of the liver, comprise approximately 10% of all hepatic cells. The role of KC in liver metastasis is not clearly understood;more specifically, it is not understood whether KC plays a defensive role against liver metastasis or enhances its angiogenesis. A better understanding of liver metastasis development and the role of KC is necessary to develop novel treatments for liver metastases. Another challenge in the treatment of cancers, including liver metastases, is the distribution of imaging and therapeutic agents to intended targets. Systemically administered drug molecules or contrast agents only reach their desired targets one part per 10,000-100,000. The overall goal of this project is to develop a broader understanding of physical barriers and biological factors involved in the progression of liver metastasis in orthotopic models of colorectal cancer and to design novel biocompatible delivery carriers able to overcome or take an advantage of these barriers with favorable pharmacokinetics and tissue distribution for highly efficient delivery of novel therapeutic agents and imaging agents. This project aims to image liver metastasis development and localization of KC in order to design an in silico model for administration of therapies and use a physical modeling process to optimize the properties of nanocarriers. Additionally, this project aims to refine, design, and evaluate biocompatibility of nanovectors for delivery of therapeutic and contrast agents for treatment of liver metastases, and to determine therapeutic and imaging efficacy of co-delivery of gold nanoparticles and cytotoxic agents from rationally designed targeted multi-stage nanovectors in in-vivo models of liver metastases.

Public Health Relevance

This project strives to image the development and progression of liver metastasis produced by colorectal cancers in orthotopic animal models and to investigate the efficiency of treatment through in silico models. A better understanding of the biology of liver metastasis will allow development of novel treatment modalities using nanotechnology, which should greatly impact public health by the elimination of liver metastasis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-9)
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Methodist Hospital Research Institute
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Martinez, Jonathan O; Evangelopoulos, Michael; Bhavane, Rohan et al. (2015) Multistage Nanovectors Enhance the Delivery of Free and Encapsulated Drugs. Curr Drug Targets 16:1582-90
Corbo, Claudia; Parodi, Alessandro; Evangelopoulos, Michael et al. (2015) Proteomic Profiling of a Biomimetic Drug Delivery Platform. Curr Drug Targets 16:1540-7
Singh, Jaykrishna; Hussain, Fazle; Decuzzi, Paolo (2015) Role of differential adhesion in cell cluster evolution: from vasculogenesis to cancer metastasis. Comput Methods Biomech Biomed Engin 18:282-92
Wang, Zhihui; Butner, Joseph D; Kerketta, Romica et al. (2015) Simulating cancer growth with multiscale agent-based modeling. Semin Cancer Biol 30:70-8
Jaganathan, Hamsa; Mitra, Sucharita; Srinivasan, Srimeenakshi et al. (2014) Design and in vitro evaluation of layer by layer siRNA nanovectors targeting breast tumor initiating cells. PLoS One 9:e91986
Yang, Yong; Wolfram, Joy; Fang, Xiaohong et al. (2014) Polyarginine induces an antitumor immune response through binding to toll-like receptor 4. Small 10:1250-4
Koshkina, Nadezhda V; Briggs, Katrina; Palalon, Flavio et al. (2014) Autophagy and enhanced chemosensitivity in experimental pancreatic cancers induced by noninvasive radiofrequency field treatment. Cancer 120:480-91
Martinez, Jonathan O; Evangelopoulos, Michael; Karun, Vivek et al. (2014) The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation. Biomaterials 35:9824-32
Gonzalez-Villasana, Vianey; Rodriguez-Aguayo, Cristian; Arumugam, Thiruvengadam et al. (2014) Bisphosphonates inhibit stellate cell activity and enhance antitumor effects of nanoparticle albumin-bound paclitaxel in pancreatic ductal adenocarcinoma. Mol Cancer Ther 13:2583-94
Koay, Eugene J; Truty, Mark J; Cristini, Vittorio et al. (2014) Transport properties of pancreatic cancer describe gemcitabine delivery and response. J Clin Invest 124:1525-36

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