John Murphy, MDLinx | September 15, 2016
Newly developed selective nanoparticles can deliver cytotoxic siRNA to kill cancer cells but leave healthy cells alone, researchers reported in a September 12, 2016 article in the Proceedings of the National Academy of Sciences.
“The discovery that nanoparticles can be selective to certain cells based only on their physical and chemical properties has profound implications for nanoparticle-based therapies because cell type specificity of drug carriers could alter patient outcomes in the clinic,” said corresponding author Daniel Siegwart, Assistant Professor of Biochemistry at University of Texas Southwestern Medical Center, in Dallas, TX.
“At the same time, a deeper understanding of nanoparticle interactions in the body opens the door to predict patient responses to existing liposome and nanoparticle therapies, and offers the potential to create future drug carriers customized according to individual genetic profiles,” Dr. Siegwart added.
For this investigation, the researchers obtained a particular pair of matched cancer/normal cell lines from a single patient. Using high-throughput library screening, the researchers identified a nanoparticle, constructed of a polymer/DNA complex, that provoked different responses from cancer cells and normal cells, even when those cells came from the lungs of the same patient.
To test this, the researchers performed experiments in which the selective nanoparticles entered and incited rapid endocytosis within cancer cells, but were immediately stopped at the membrane of normal cells.
“These functional polyester nanoparticles provide an exciting alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies,” said co-author John Minna, MD, Professor and Distinguished Chair in Molecular Pulmonary Oncology at UT Southwestern.
When injected into tumors in mice, the drug-carrying cancer-selective nanoparticles were retained for more than a week, while nonselective nanoparticles used as controls were cleared within hours. This translated to improved siRNA-mediated cancer cell apoptosis and significant suppression of tumor growth, the researchers noted.
“The ability to specifically target cancer cells using nanoparticles could alter how we administer drugs to patients,” said Dr. Minna, who is also Director of the Hamon Center for Therapeutic Oncology Research. “It is already possible to use genetic sequencing to customize drug regimens for each patient. We may also be able to customize the drug carrier to predictably improve patient responses.”