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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143837-05
Application #
8379714
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2012-09-24
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$867,742
Indirect Cost
$423,118
Name
Methodist Hospital Research Institute
Department
Type
DUNS #
185641052
City
Houston
State
TX
Country
United States
Zip Code
77030
Pandolfi, Laura; Minardi, Silvia; Taraballi, Francesca et al. (2016) Composite microsphere-functionalized scaffold for the controlled release of small molecules in tissue engineering. J Tissue Eng 7:2041731415624668
Ware, Matthew J; Keshishian, Vazrik; Law, Justin J et al. (2016) Generation of an in vitro 3D PDAC stroma rich spheroid model. Biomaterials 108:129-42
Lapin, Norman A; Krzykawska-Serda, Martyna; Ware, Matthew J et al. (2016) Intravital microscopy for evaluating tumor perfusion of nanoparticles exposed to non-invasive radiofrequency electric fields. Cancer Nanotechnol 7:5
Tanei, Tomonori; Leonard, Fransisca; Liu, Xuewu et al. (2016) Redirecting Transport of Nanoparticle Albumin-Bound Paclitaxel to Macrophages Enhances Therapeutic Efficacy against Liver Metastases. Cancer Res 76:429-39
McConnell, Kellie I; Shamsudeen, Sabeel; Meraz, Ismail M et al. (2016) Reduced Cationic Nanoparticle Cytotoxicity Based on Serum Masking of Surface Potential. J Biomed Nanotechnol 12:154-64
Scott, Bronwyn; Shen, Jianliang; Nizzero, Sara et al. (2016) A pyruvate decarboxylase-mediated therapeutic strategy for mimicking yeast metabolism in cancer cells. Pharmacol Res 111:413-21
Mi, Yu; Mu, Chaofeng; Wolfram, Joy et al. (2016) A Micro/Nano Composite for Combination Treatment of Melanoma Lung Metastasis. Adv Healthc Mater 5:936-46
Corbo, Claudia; Molinaro, Roberto; Parodi, Alessandro et al. (2016) The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery. Nanomedicine (Lond) 11:81-100
Liu, Zongbin; Han, Xin; Qin, Lidong (2016) Recent Progress of Microfluidics in Translational Applications. Adv Healthc Mater 5:871-88
Leonard, Fransisca; Godin, Biana (2016) 3D In Vitro Model for Breast Cancer Research Using Magnetic Levitation and Bioprinting Method. Methods Mol Biol 1406:239-51

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