“Nanoparticles Seek and Destroy Glioblastoma in Mice”

Researchers created a nanosystem comprised of a nanoparticle and two peptides that can travel through the bloodstream selectively to cancerous cells and kill them. Apparently it was able to cure 9/10 glioblastoma-suffering mice on which it was tested (in one of the two models they tested). 

Glioblastoma is a type of relatively prevalent and very dangerous brain cancer, involving glia, a type of brain cell that plays Robin to neurons’ Batman. Glia are thought of as support cells to neurons, which do the actual signaling in the nervous system. There are about the same number of glia in the human nervous system as there are neurons. 

Peptide is a term for a series of amino acids not quite big enough to be called a protein. Amino acids are small molecules that are the building blocks of proteins, but their naming conventions have always been a bit arbitrary to me (and to my relief Wikipedia agrees): two amino acids form a dipeptide, more are a polypeptide, anything in that arena is a peptide, and longer sequences are a protein, or subunits of a protein (sometimes proteins are formed by a bunch of amino acid sequences coming together like Voltron). In short, peptide just means a molecule made up of the same stuff as proteins. 

From Science Daily:

Rather than presenting as a well-defined tumor, glioblastoma will often infiltrate the surrounding brain tissue, making it extremely difficult to treat surgically or with chemotherapy or radiation. Likewise, several mouse models of glioblastoma have proven completely resistant to all treatment attempts. In a new study, a team led by scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) and the Salk Institute for Biological Studies developed a method to combine a tumor-homing peptide, a cell-killing peptide, and a nanoparticle that both enhances tumor cell death and allows the researchers to image the tumors.

The nanosystem developed in this study is made up of three elements. First, a nanoparticle acts as the carrier framework for an imaging agent and for two peptides (short proteins). One of these peptides guides the nanoparticle and its payload specifically to cancer cells and the blood vessels that feed them by binding cell surface markers that distinguish them from normal cells. This same peptide also drives the whole system inside these target cells, where the second peptide wreaks havoc on the mitochondria, triggering cellular suicide through a process known as apoptosis.

Together, these peptides and nanoparticles proved extremely effective at treating two different mouse models of glioblastoma. In the first model, treated mice survived significantly longer than untreated mice. In the second model, untreated mice survived for only eight to nine weeks. In sharp contrast, treatment with this nanosystem cured all but one of ten mice. What’s more, in addition to providing therapy, the nanoparticles could aid in diagnosing glioblastoma; they are made of iron oxide, which makes them — and therefore the tumors they target — visible by MRI, the same technique already used to diagnose many health conditions.

Using iron to make specific cells visible to MRI – sounds familiar, no? I wonder if that other group had considered using a nanoparticle delivery system to track neuroblasts; I imagine it’s more of a short-term solution though, compared to the long-term tracking they achieve through gene therapy, and it’s unclear if neuroblasts could be identified by a comparable system in any case. 

They mentioned mitochondria: a mitochondrion is the organelle (cellular subunit) where energy is basically produced from sugar and oxygen. The cell needs it for energy, so if a cell’s mitochondria get knocked out (as they do by this nanosystem), the cell is toast and will destroy itself in an orderly fashion, called apoptosis

In a final twist, the researchers made the whole nanosystem even more effective by administering it to the mice in conjunction with a third peptide. Dr. Ruoslahti and his team previously showed that this peptide, known as iRGD, helps co-administered drugs penetrate deeply into tumor tissue. iRGD has been shown to substantially increase treatment efficacy of various drugs against human breast, prostate, and pancreatic cancers in mice, achieving the same therapeutic effect as a normal dose with one-third as much of the drug. Here, iRGD enhanced nanoparticle penetration and therapeutic efficacy.

So, this is cool. However, it seems like their main focus was on whether or not, and for how long, the mice survived – a good starting point, for sure, but not nearly enough to show that this system is effective. There’s nothing to show that this system is actually specific – that it’s not also killing the healthy cells around the cancerous cells. That might require a different approach – maybe cutting up the mice brains afterwards, checking for extraneous damage and whatnot. If it kills tumors but causes severe brain damage… well, hell, it’s still probably better than the alternative, but it has to be known. 

My final question is whether or not glioblastoma is the only type of cancer that has easily-identifiable cancer cells (to a nanosystem). Is this a potential solution to a particular type of cancer, or to a broad swath of it? I’m guessing they’d be the first to pronounce if it was the latter case, but in any case we can still hope more advancements like this are made in the future; it sounds promising.

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