Jinjun Shi, PhD, of the Department of Anesthesiology, Perioperative and Pain Medicine, and his colleagues have developed a new platform that uses nanoparticles to systemically deliver small interfering RNA (siRNA) to solid tumors. In a paper published in PNAS, the researchers report using the nanoparticle platform to validate Proibitin1 (PHB1) as a therapeutic target for non-small cell lung cancer (NSCLC) and describe the platform’s potential for use in validating other potential cancer targets and in developing new cancer therapies.

The lipid-polymer hybrid nanoparticles used in the new platform efficiently encapsulate siRNA, releasing it slowly overtime, resulting in a sustained release and gene silencing.

“By rational design and optimization, these nanoparticles can circulate in the bloodstream for a relatively long period of time, allowing them to leak out of the tumor microvasculature to entering tumor tissue,” said Shi.

The long-circulating siRNA nanoparticles can potentially silence any gene of interest, allowing researchers to explore and/or confirm the role of potential gene targets. In collaboration with Bruce R. Zetter, PhD, from Boston Children’s Hospital, the BWH team reports on applying the new platform to a potential therapeutic target in lung cancer. No specific and effective inhibitors against PHB1 currently exist, which means that up until now, it has not been possible to thoroughly test PHB1’s role. When the team “silenced” PHB1 using the nanoparticle platform, they saw a marked decrease in tumor growth in preclinical models. The team also found that higher levels of PHB1 in tumor tissue were associated with poorer overall survival in patients with NSCLC.

The team is planning to evaluate PHB1 further, and will also explore other potential therapeutic targets, particularly those considered “undruggable,” for cancer treatment. The team is also interested in applying the platform to address other biomedical problems such as inflammatory diseases.

“Our platform has many promising features for clinical development, including long blood circulation, high tumor accumulation, effective gene silencing, negligible in vivo side effects, long shelf-life, and a simple, scalable formulation strategy,” said Shi.