Researchers from Northwestern Medicine have developed lipid polymer-based nanoparticles that target key cancer drivers, called brain tumor initiating cells, in a mouse model of glioblastoma brain tumors.
“BTICs are malignant brain tumor populations that underlie the therapy resistance, recurrence and unstoppable invasion commonly encountered by glioblastoma patients after the standard treatment regimen of surgical resection, radiation and chemotherapy,” first author Dr. Dou Yu said in prepared remarks.
The team’s study was published in the journal Proceedings of the National Academy of Sciences.
The researchers prepared mouse models of brain tumors using BTICs derived from human patients. Then, they injected small interfering RNA nanoparticles directly into the tumor. These short sequences of RNA limit the expression of cancer-promoting proteins, according to the researchers.
Part of what makes glioblastoma so challenging to treat is that its genetic makeup is different for each patient. The Northwestern team said its therapy could pave the way for personalized treatment, since siRNAs can target multiple cancer-causing gene products simultaneously.
The team evaluated siRNAs targeting four transcription factors that are expressed in many, but not all, glioblastoma tissues. They observed that the therapy was successful against glioblastoma BTICs with high levels of those four transcription factors, but other classes of the cancer did not respond.
In the preclinical model, the nanotechnology halted tumor growth and even extended survival after it was continuously administered using an implanted drug infusion pump.
“This major progress, although still at a conceptual stage, underscores a new direction in the pursuit of a cure for one of the most devastating medical conditions known to mankind,” Yu added.
The researchers stressed that this is an early, proof-of-concept study. They will need to evaluate its long-term safety before they can bring it into the clinic.
“This paints a picture for personalized glioblastoma therapy regimens based on tumor profiling,” Yu said. “Customized nanomedicine could target the unique genetic signatures in any specific patient and potentially lead to greater therapeutic benefits.”