Tumor imaging and interferon-g-inducible protein-10 gene transfer using a highly efficient transferrin-conjugated liposome system in mice

摘要

Purpose: We have developed a PEGylated transferrin-conjugated liposomes (PTf-Ls) system for the combined tumor imaging and targeted delivery of the IFN-g-inducible protein-10 (IP-10) gene in a single macromolecular construct. Here, we characterize and analyze the use of this system in a mouse model of breast cancer. Experimental Design: The biophysical and cell transfection properties of PTf-Ls were determined through a series of in vitro experiments. A nude mouse/breast cancer cell line xenograft model (mouse xenograft model) was used to image the tumor internalization of fluorescently labeled PTf-Ls. The clinical use of the system was tested by treating tumor-bearing mice with PTf-Ls loaded with IP-10 plasmid DNA or fluorescent lipoplexes. Results: The resulting 165-nm liposomes (zeta potential=10.6 mV) displayed serum resistance, low cytotoxicity (5%), and high transfection efficiency (82.8%) in cultured cells. Systemic intravenous administration of fluorescent PTf-Ls in the mouse xenograft model resulted in nanoparticle circulation for 72 hours, as well as selective and efficient internalization in tumor cells, according to in vivo fluorescence and bioluminescence analyses. Tumor fluorescence increased gradually up to 26 hours, whereas background fluorescence decreased to near-baseline levels. Treatment of mice with PTf-Ls entrapped pcDNA3.1-IP-10 suppressed tumor growth in mice by 79% on day 50 and increased the mean survival time of mice. Fluorescent pcDNA-IP-10-entrapped PTf-Ls showed good properties for simultaneous tumor-targeted imaging and gene-specific delivery in an animal tumor model. Conclusions: Our developed transferrin-conjugated liposome system possesses promising characteristics for tumor-targeting, imaging, and gene therapy applications.