The nanoparticles can be freeze-dried and stored for up to three months before use.
The shelf-stable particles may obviate the need for virus-mediated gene therapy, which has been associated with safety concerns, the scientists say.
‘Most non-viral gene therapy methods have very low efficacy,’ says Jordan Green, an assistant professor of biomedical engineering at Johns Hopkins. ‘Nanoparticle-based gene therapy has the potential to be both safer and more effective than conventional chemical therapies for the treatment of cancer.’
To develop the nanoparticle, Green's team procured small molecules and mixed combinations together to generate chemical reactions that resulted in different polymers.
Each different polymer was mixed with DNA that encodes a fluorescent protein, thereby making the DNA to attach to the polymers and produce the nanoparticles.
They added each sample to human brain tumour cells and stem cells. After 48 hours, they counted how many cells glowed by absorbing the nanoparticles and produced the fluorescent protein encoded by the DNAs that were induced into the cell.
The researchers found that one particular formulation of so-called poly(beta-amino ester) nanoparticles did particularly well at getting into both glioblastoma and brain tumour stem cells.
They freeze-dried these nanoparticles and stored them at different temperatures (freezer, refrigerator and room temperature) for different lengths of time (one, two and up to three months), and then retested their ability to get into cells.
Green says after six months in storage, the effectiveness dropped by about 50%, but at up to three months of storage at room temperature there was virtually no change in effectiveness.
The team also found that certain nanoparticles had a particular affinity for brain tumour cells over healthy brain cells.
‘I could imagine particles based on this technology being used in conjunction with, and even instead of brain surgery,’ says Alfredo Quinones-Hinojosa, an associate professor of neurosurgery and oncology at Johns Hopkins.
‘I envision that one day, as we understand the etiology and progression of brain cancer, we will be able to use these nanoparticles even before doing surgery. How nice would that be? Imagine avoiding brain surgery altogether.’
The Institute for NanoBioTechnology at The Johns Hopkins University, the Maryland Stem Cell Research Fund, National Institutes of Health, the Howard Hughes Medical Institute and the Robert Wood Johnson Foundation funded the study.
The report appears in the August issue of Biomaterials.