Scientists from Harvard Medical School and West China School of Pharmacy have developed a unique nanoparticle platform which utilizes a kind of molecular shell made of Cationic polymer lipids and Lipid – polyethylene glycol carries siRNA as a transportation system. This study was published in PNAS.

With the capability to silence any gene of interest, RNA interference (RNAi) technology has demonstrated enormous potential in medical research and applications. RNAi-dediated gene silencing has revealed the functionality of specific genetic alterations in cancers. Many of these genes and pathways are considered “undruggable” targets or require complex and time-consuming development of effective inhibitors. The ubiquitous application of RNAi in cancer research and therapy is nevertheless hindered by the challenge of effective systemic in vivo delivery of siRNA to tumors, which requires overcoming of multiple physiological barriers, such as enzymatic mononuclear phagocyte system (MPS), and poor cellular uptake and endosomal escape.

In this study, researchers developed a new generation lipid-polymer hybrid nanoparticle platform for effective systemic delivery of small interfering RNA (siRNA) to tumors, which represents a challenging hurdle for the widespread application of RNA interference (RNAi) in cancer research and therapy. With promising in vivo features such as long blood circulation, high tumor accumulation, and effective gene silencing, the hybrid siRNA nanoparticles were successfully used to reveal and validate a putative therapeutic target. Prohibitin1 (PHB1), in non-small cell lung cancer treatment. In vivo antitumor efficacy results and human tissue microarray analysis further suggested the feasibility of utilizing PHB1 siRNA nanoparticles as a novel therapeutic agent.

This hybrid RNAi nanoparticle platform may serve as a valuable tool for validating potential cancer targets and developing new cancer therapies.