Brain tumors are not inherently more resistant to treatment than other cancers, but their location, protected by the skull and the blood-brain barrier, makes it challenging to target them effectively. In an attempt to deliver drugs inside glioma tumors, researchers at Tel Aviv University in Israel used lipid nanoparticles to ferry RNA interference (RNAi) molecules into tumor cells.
RNAi has been used in the past to halt the growth of cancers, but the new approach may allow its use for brain cancers. The lipid-based particles were coated with polysugar hyaluronan (HA), a substance that sticks to receptors only found on glioma cells. In pre-clinical testing using mice with human glioma implanted in their brains, the researchers showed that 60% of mice dosed with the new therapy lived for at least 100 days post-treatment. The control group that received traditional chemo lived for only a third of that.
Some details from the study abstract in ACS Nano:
Herein, we devised a localized strategy to deliver RNA interference (RNAi) directly to the GBM site using hyaluronan (HA)-grafted lipid-based nanoparticles (LNPs). These LNPs having an ionized lipid were previously shown to be highly effective in delivering small interfering RNAs (siRNAs) into various cell types. LNP’s surface was functionalized with hyaluronan (HA), a naturally occurring glycosaminoglycan that specifically binds the CD44 receptor expressed on GBM cells. We found that HA-LNPs can successfully bind to GBM cell lines and primary neurosphers of GBM patients. HA-LNPs loaded with Polo-Like Kinase 1 (PLK1) siRNAs (siPLK1) dramatically reduced the expression of PLK1 mRNA and cumulated in cell death even under shear flow that simulate the flow of the cerebrospinal fluid compared with control groups. Next, a human GBM U87MG orthotopic xenograft model was established by intracranial injection of U87MG cells into nude mice. Convection of Cy3-siRNA entrapped in HA-LNPs was performed, and specific Cy3 uptake was observed in U87MG cells. Moreover, convection of siPLK1 entrapped in HA-LNPs reduced mRNA levels by more than 80% and significantly prolonged survival of treated mice in the orthotopic model. Taken together, our results suggest that RNAi therapeutics could effectively be delivered in a localized manner with HA-coated LNPs and ultimately may become a therapeutic modality for GBM.