Biodegradable Cationic Nanoparticles as a Push Chemodrug Carrier and a Pull cfDNA Scavenger Against Breast Cancer Metastasis
Abstract
The goal of this project is to develop a novel therapeutic approach for the prevention of breast cancer metastasis, by using nucleic acid binding nanoparticles (NABNPs) designed to deliver high payloads of cytotoxic drugs to tumor tissues, while simultaneously scavenging the pro-inflammatory cell-free DNA (cfDNA) that is released in the blood circulation as a result oftumor progression and/or destruction by chemotherapy. This is a collaborative research project conducted in partnership by two teams, supported by two distinct awards (BC180904, BC180904P1). Among the key aims of the research supported by this award (BC180904P1, partnering team) is the development of experimental models that enable the visualization and quantification of breast cancer dissemination in live animals, using non-invasive imaging techniques that can detect biox2;luminescent signals from live cancer cells, and compare them over time, in order to obtain longitudinal measurements of both the anatomical location and overall burden of metastatic tissue. During the first year of the award, we engineered multiple triple negative breast cancer (TNBC) cell lines with different lentivirus constructs, each encoding for both fluorescent (EGFP, ZsGreen) and bioluminescent reporters (different variants of Luciferase from the firefly Photinus pyralis). We then compared the performance of the various lentivirus constructs in terms of sensitivity and stability of expression over time, in both mouse and human TNBC cells, in vitro and in vivo. Our experiments led to the generation of 3 independent TNBC cell lines (1 murine, 2 human) expressing high levels of both ZsGreen and Luciferase (Photinus pyralis), and can be efficiently monitored in terms of longitudinal growth and spontaneous metastatic dissemination in live animals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1130804
Entities
People
- Piero Dalerba
Organizations
- Columbia University