Viral protein–and-dye combo destroys tumors in mice

A nanoparticle made of virus coat proteins decorated with dye molecules allows lasers to blast tumor cells and then invites the immune system to mop up the mess (J. Am. Chem. Soc. 2021, DOI: 10.1021/jacs.1c05090). The approach adds a powerful new twist to photothermal therapy, an experimental cancer treatment that attempts to destroy tumor cells using heat generated from light.

Photothermal therapy generally injects inorganic nanoparticles, such as gold nanorods, into a tumor and then heats the particles with lasers to destroy the tumor cells in a localized manner. The cell debris then activates the immune system, causing it to attack what’s left of the tumor. But in most studies so far, this one-two punch isn’t quite strong enough and often leaves behind cancer cells that can metastasize. What’s more, gold can be toxic when it accumulates in the body.

Arezoo Shahrivarkevishahi, a graduate student in the lab of chemist Jeremiah Gassensmith at the University of Texas at Dallas, and her colleagues instead turned to viruslike particles (VLPs)—structures made from virus proteins but lacking viral genetic material. They produced VLPs by repurposing proteins from the bacteriophage Qβ that self-assemble to form the virus’s coat. Then, by modifying functional groups on the proteins, they decorated the surface of each particle with an average of 212 molecules of croconium dye, which is nontoxic and absorbs near-infrared light. That much dye “can generate a lot of heat,” Shahrivarkevishahi says.

Not only is the resulting particle biocompatible, she says, but because it mimics viruses and is recognized by the immune system, it may produce a stronger immunogenic response than phototherapy using inorganic particles. The researchers also found that tumor cells take up the nanoparticle twice as efficiently as dye alone.

The team injected the particles into breast tumor cells implanted into the mammary glands of mice and then applied near-infrared laser light to the skin over the tumor to activate the therapy. Mice who received this combination treatment—VLPs decorated with dye—showed a 70% reduction in primary tumors, an 85% reduction in metastases, and a 30% increase in survival compared with mice that received control injections of saline. The particles also did better at reducing tumors than either naked VLPs or dye alone.

Though the work is still preliminary, combining a dye with a VLP “is a great idea,” says M.G. Finn, a biological chemist at the Georgia Institute of Technology, who was not involved in the research. “It adds very nicely to the library of uses for VLPs and self-assembled nanoparticles.”

“The good thing about viruses is that we can not only decorate their surfaces but also load things inside them,” Shahrivarkevishahi says. Although the current study presents a simple version of the approach, loading Qβ coat proteins or another VLP with chemotherapy or other cancer drugs could further potentiate the treatment’s efficacy.