Engineering an “Invisible Cloak” for Bacteria to Deliver Cancer Drugs

Scientists exploring a novel but highly promising avenue of cancer treatment have developed a type of “invisibility cloak” that helps engineered bacteria sneak through the body’s immune defenses. The result is more powerful delivery of anti-cancer drugs and shrinking of tumors in mice, with the scientists hopeful the approach can overcome toxicity issues that have plagued these techniques so far.

Traditional forms of cancer treatment – radiotherapy, chemotherapy and immunotherapy – each have their own strengths when it comes to combating tumors, and what’s known as therapeutic bacteria could bring its own set of skills into the mix. Bacteria itself can have powerful anti-tumor effects, but genetic engineering could allow it to take on entirely new capabilities, including releasing specific compounds or carrying potent anti-cancer drugs. There are a number of challenges in using bacteria for this purpose, however, with the issue of toxicity chief among them. Living bacteria can grow rapidly in the body, and because the body’s immune system sees them as a threat, too many can trigger an extreme inflammatory response.

In clinical trials, these toxicities have been shown to be the critical problem, limiting the amount we can dose bacteria and compromising efficacy,” said Columbia University‘s Jaeseung Hahn, who co-led the research. “Some trials had to be terminated due to severe toxicity.

Addressing this toxicity problem would mean finding (or engineering) bacteria that can evade the body’s immune system and safely make it to a tumor to fulfill their anti-cancer potential. Hahn’s team has made new inroads in this space by turning to sugar polymers called capsular polysaccharides (CAP), which naturally coat bacterial surfaces and protect them from immune attacks.

We hijacked the CAP system of a probiotic E. coli strain Nissle 1917,” said Tetsuhiro Harimoto, the study’s co-lead author. “With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch.”

Source: https://www.engineering.columbia.edu/

Stronger than Steel, Tougher than Kevlar

Spider silk is said to be one of the strongest, toughest materials on the Earth. Now engineers at Washington University in St. Louis have designed amyloid silk hybrid proteins and produced them in engineered bacteria. The resulting fibers are stronger and tougher than some natural spider silks.

To be precise, the artificial silk — dubbed “polymeric amyloid” fiber — was not technically produced by researchers, but by bacteria that were genetically engineered in the lab of Fuzhong Zhang, a professor in the Department of Energy, Environmental & Chemical Engineering in the McKelvey School of Engineering.

Zhang has worked with spider silk before. In 2018, his lab engineered bacteria that produced a recombinant spider silk with performance on par with its natural counterparts in all of the important mechanical properties.

After our previous work, I wondered if we could create something better than spider silk using our synthetic biology platform,” Zhang said.

The research team, which includes first author Jingyao Li, a PhD student in Zhang’s lab, modified the amino acid sequence of spider silk proteins to introduce new properties, while keeping some of the attractive features of spider silk.

A problem associated with recombinant spider silk fiber — without significant modification from natural spider silk sequence — is the need to create β-nanocrystals, a main component of natural spider silk, which contributes to its strength. “Spiders have figured out how to spin fibers with a desirable amount of nanocrystals,” Zhang said. “But when humans use artificial spinning processes, the amount of nanocrystals in a synthetic silk fiber is often lower than its natural counterpart.

Their research was published in the journal ACS Nano.

Source: https://source.wustl.edu/