Principal investigator Xiaoming (Shawn) He.Researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and the Richard J. Solove Research Institute (OSUCCC – James) have developed cancer-killing nanoparticles that swell and burst when exposed to near-infrared laser light. The researchers report this work in a paper in Advanced Materials.
Such 'nanobombs' might overcome a biological barrier that has blocked development of agents that work by altering the activity of genes in cancer cells, either killing the cells outright or stalling their growth. Agents that change gene expression are generally forms of RNA (ribonucleic acid), and they are notoriously difficult to use as drugs, mainly because they are readily degraded when free in the bloodstream.
One way to solve this problem is to package the RNA in nanoparticles that target tumor cells, but this leads to a second problem. When cancer cells take up ordinary nanoparticles, they often enclose them in small compartments called endosomes. This prevents the drug molecules from reaching their target, and they are soon degraded.
So in addition to RNA, the new nanobombs contain ammonium bicarbonate, a leavening agent sometimes used in baking, which vaporizes when exposed to near-infrared laser light. This causes the nanobombs to swell to over three times their original size, bursting the endosomes and dispersing the RNA agent into the cell.
"A major challenge to using nanoparticles to deliver gene-regulating agents such as microRNAs is the inability of the nanoparticles to escape the compartments, the endosomes, that they are encased in when cells take up the particles," explains principal investigator Xiaoming (Shawn) He, associate professor of biomedical engineering and member of the OSUCCC – James Translational Therapeutics Program. "We believe we've overcome this challenge by developing nanoparticles that include ammonium bicarbonate, a small molecule that vaporizes when exposing the nanoparticles to near-infrared laser light, causing the nanoparticle and endosome to burst, releasing the therapeutic RNA."
To test the nanobombs, He and his colleagues tried them out on prostate tumors in an animal model. The nanoparticles were equipped to target cancer stem-like cells (CSCs), which are cancer cells that have properties of stem cells. CSCs often resist therapy and are thought to play an important role in cancer development and recurrence.
The therapeutic agent in the nanoparticles was a form of microRNA called miR-34a. The researchers chose this molecule because it can lower the levels of a protein that is crucial for CSC survival and may also be involved in the development of resistance to chemotherapy and radiation therapy. They found that the nanobombs successfully delivered miR-34a to the tumors, significantly reducing their size.
The advantage of using near-infrared laser light is that it can penetrate tissue to a depth of 1cm. For deeper tumors, the light would be delivered using minimally invasive surgery.
This story is adapted from material from OSUCCC – James, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.