Scientists drop nanoparticle 'cluster bombs' on cancer cells

Scientists have devised a nanoparticle “cluster bomb” that progressively breaks down in size to penetrate tumors and deliver the chemotherapy drug cisplatin to cancer cells, according to a study published online March 28, 2016 in the journal Proceedings of the National Academy of Sciences.

Although cisplatin has been used as a chemotherapeutic agent for decades, its toxic side effects undercut its effectiveness.

“The negative side effects of cisplatin are a long-standing limitation for conventional chemotherapy,” said co-lead author Jinzhi Du, PhD, postdoctoral fellow in the Department of Biomedical Engineering at Emory University and Georgia Institute of Technology, in Atlanta, GA.

“In our study, the delivery system was able to improve tumor penetration to reach more cancer cells, as well as release the drugs specifically inside cancer cells through their size-transition property,” Dr. Du said.

In this delivery system, the clustered nanoparticle begins relatively large in size—about 100 nm—to achieve longer circulation and selective extravasation through tumor vascular fenestrations.

But once the nanoparticle docks at tumor sites, the acidic conditions there trigger it to break down and release smaller prodrug “bomblets”—just 5 nm—to penetrate into tumors to reach more cancer cells.

Once inside tumor cells, the prodrug particles undergo further cellular breakdown to release active cisplatin, which kills cancer cells by crosslinking and damaging DNA.

In in vivo experiments, the researchers showed that their clustered nanoparticles could enhance cisplatin drug accumulation in tumor tissues. When mice bearing human pancreatic tumors were given the same doses of free cisplatin or cisplatin robed in pH-sensitive nanoparticles, the level of platinum was 7 times higher in the tumor tissues targeted by the clustered nanoparticles. This suggests that nanoparticle delivery of a limited dose of cisplatin could restrain the toxic side effects during cancer treatment, the researchers noted.

The researchers also showed that the clustered nanoparticles were effective in mice against a cisplatin-resistant lung cancer model and an invasive metastatic breast cancer model. In the lung cancer model, a dose of free cisplatin inhibited growth by only 10%. However, the same dose contained in clustered nanoparticles inhibited growth by 95%, the researchers reported.

In the metastatic breast cancer model, treating mice with nanoparticle-robed cisplatin prolonged their survival by weeks; 50% of the mice treated with the nanoparticle delivery system were surviving at 54 days compared with 37 days for the same dose of free cisplatin. 

The nanoparticle’s enhanced efficacy in these three different tumor models suggests that this strategy may be applicable to several types of cancer, Dr. Du said.