There are many tools cancer relies on to survive and thrive, and therefore many possibilities when it comes to thwarting its advances. One such avenue centers on cellular garbage disposal units known as lysosomes, which are particularly vulnerable in cancer cells as opposed to healthy ones. And perhaps even more so now, with scientists in South Korea finding they can deliver a fatal blow to cancer cells through a careful mix of charged nanoparticles.
Lysosomes are tiny sacs packed with enzymes and acids that degrade unwanted parts of the cell, before either recycling them or dumping them outside the cell walls, much like you'd take your trash out to the curb. Recent research has suggested lysosomes could play a role in Alzheimer's, where a dysfunctional disposal system can enable the buildup of toxic proteins in the brain.
Scientists at South Korea's Institute of Basic Science are working to instigate their own type of dysfunctional lysosomes, the reason being that a compromised lysosome that releases its trash inside the cell can cause that cell to die, which is obviously a good thing when we're talking about cancer cells.
One thing working in the team's favor is the fact that cancer cells' lysosomes are easier to damage than those of healthy cells. The trouble has been coming up with therapies that target only the former, and leave the latter intact.
The researchers believe they have found a way to achieve this, and it involves a delicate mix of negatively and positively charged nanoparticles. These selectively form in clusters on the cancer cell surface, which then transform into nanoparticles crystals inside the lysosomes and cause them to swell, gradually deteriorate and eventually die.
"In this work, we have harnessed the deregulated waste management system of the cancer cells to act as a 'nanoscale assembly line' for constructing high-quality nanoparticle crystals that destroy the very lysosome 'reactors' that allowed them to grow in the first place," says Bartosz A. Grzybowski, co-leading author of the study.
The team experimented with different recipes for this novel form of therapy, finding that nanoparticles featuring 80 percent positively charged and 20 percent negatively charged ligands were optimal for cancer cell selectivity. The team also believes a pH sensitivity on part of the negatively charged ligands is key to the cancer cell selectivity. This was established through experiments on a range of cancer cell types, with the team's nanoparticles proving effective against all of them.
"Our conclusions are based on a comparison of 13 different sarcomas, melanoma, breast and lung carcinoma cell lines with four non-cancer cell types," adds the first author of the study, Magdalena Borkowska. "The nanoparticles were effective against all 13 cancer lines, while not harming non-cancerous cells."
From here, the team aims to see if this mixed-charge strategy could be effective against tumors in animal models.
The research was published in the journal Nature Nanotechnology.
Source: Institute of Basic Science
