Functional Polyesters Deliver siRNA Drugs Selectively to Lung Cancer Cells

Researchers in Texas are now reporting they have developed drug-loaded synthetic nanoparticles that can distinguish lung cancer cells from healthy cells. 

A recent study published in the Proceedings of the National Academy of Sciences, they report they employed a patient-derived pair of matched cancer/normal cell lines, and discovered selective nanoparticles that may deliver a cytotoxic small interfering RNA (siRNA) to kill cancer cells and not normal cells. The investigators report that cells responding differently to the same nanoparticle could have profound implications for gene therapy.

“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 co-study author Daniel Siegwart, PhD, who is an Assistant Professor of Biochemistry at the University of Texas (UT) Southwestern Medical Center, in a news release. “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 and his colleagues hypothesize that functional polyester nanoparticles may provide an exciting alternative approach for selective drug delivery. Through the use of functional polyesters, tumor cells could be targeted in a new way that reduces many of the adverse side effects associate with current cancer therapies. 

It is now common to use genetic sequencing to customize drug regimens for each patient. The team theorizes that it may possible to customize the drug carrier to predictably improve patient responses.

The researchers developed new chemical reactions to create a diverse library of polymers that could deliver nucleic acid drugs. After testing hundreds of polymers, they found that cells could respond differently to the same drug carrier, even when those cancerous and normal cells came from the lungs of the same patient.

In this study, the researchers delivered siRNA-based drugs to disrupt the functioning and growth of tumor cells by eliminating the proteins the cells need to survive. They found that the cancer selective nanoparticles stayed inside of tumors in mice for more than one week. However, nonselective control nanoparticles were cleared within a few hours. This translated to improved siRNA-mediated cancer cell death and significant suppression of tumor growth.

Knowing that different cells could respond differently to the same drug carrier opens up a new view on nanoparticles. The authors report this could change how investigators consider the design and evaluation of all nanoparticle carriers.