A team of University of Chicago chemists and biologists developed a tiny device made out of DNA intended to locate tumor cells and force them to reveal themselves to patrolling immune cells.
Early tests at UChicago show promise for treating resistant tumors with this unique approach
One of the most promising avenues in treating cancer is to restore our immune system’s ability to recognize and attack cancerous cells. A team of University of Chicago chemists and biologists developed a tiny device that can locate tumor cells and force them to reveal themselves to patrolling immune cells. In tests with mice, this resulted in tumor regression.
“When it comes to drug delivery, the problem, as molecular biologist Inder Verma put it, is delivery, delivery, and delivery,” explained Yamuna Krishnan, a professor in the Department of Chemistry and an author of the study. “These DNA nanodevices now make drug delivery hyperspecific, allowing us to think of ways to treat cancer without killing the cell that the therapeutic is delivered to.”
The focus of these nanodevices is a particular type of cell known as tumor-associated macrophages, or TAMs. Macrophages are a type of immune cell that normally is supposed to recognize and remove microbes, cellular debris, and other foreign substances from cells; but if something goes wrong with them, they can become a key part of cancerous tumors. TAMs can comprise up to 50% of tumor mass in triple-negative breast cancer.
However, “despite the high abundance of TAMs in solid tumors, mechanisms underlying their impact on tumor development and therapeutic strategies to target them are incompletely understood,” said study co-author Lev Becker, associate professor in the Ben May Department for Cancer Research.
The importance of these TAMs goes back to how the immune system recognizes cancerous cells. There is a subpopulation of immune cells called CD8+ T cells that are critical in recognizing and killing cancerous cells. These CD8+ T cells can be activated against threats by binding to molecular structures called “antigens” on the surface of cancerous macrophages. This strategy goes awry, however, when TAMs don’t present antigens, so there is nothing for the T-cells to recognize.
Becker’s group found that TAMs harbored a high level of a kind of enzyme called cysteine proteases. They knew these particular enzymes live in lysosomes, which work as the “stomach” of the cell, so Becker’s insight was that they might be “over-digesting” tumor antigens –thereby concealing cancerous cells from patrolling CD8+ T cells.
To test this idea, Becker’s group needed to prove that the problem really did lie in the lysosomes eating away at the antigens. So they used mice whose macrophages lacked a protein that regulates lysosomal enzyme levels and activity. They found that indeed, the lysosomes in the TAMs of these mice weren’t destroying antigens as much. This ultimately allowed CD8+ T cells to “see” and attack the tumor.
Next, they needed to figure out a way to target this process therapeutically.
Meanwhile, Krishnan, an expert in DNA nanotechnology, had recently developed the expertise to send tiny nanodevices made out of DNA directly to the lysosomes of specific immune cells in model organisms such as worms and zebrafish. The two labs teamed up to overcome this challenge.
Kasturi Chakraborty, a former grad student of the Krishnan lab and now a postdoctoral scholar in Becker’s lab, developed a tiny DNA nanodevice that delivered a cysteine protease inhibitor. When Chang Cui, a graduate student in the Becker lab, injected it into a mouse with a tumor, this nanodevice preferentially targeted lysosomes inside TAMs, where it stopped the enzymes from destroying antigens—rendering them once again “visible” to patrolling immune cells.
Combining this DNA nanodevice with frontline chemotherapy led to sustained tumor regression in a triple-negative-breast-cancer model in tests with mice. This outcome was exciting because this type of cancer is particularly difficult to treat.
It’s also a fundamentally different approach from the standard way that researchers think about treating cancer: “When we target a drug, success usually means you have killed the cell you wanted to target,” said Krishnan. “However, in our approach, our intent was not to kill the target cells, but rather reprogram them and change their character. Once the nanodevice flips the switch in a TAM, natural immunity takes care of the rest.”
The researchers hope that this new organelle-specific delivery using DNA nanodevices is the next generation of drug targeting.
It could even go beyond cancer, because specific delivery to macrophages could impact a broad range of diseases where immunity has gone awry, the scientists said.
“You wouldn’t see this work in just a chemistry lab or just an immunology lab,” said Chakraborty. “At UChicago, chemists and biologists are in the same building, so there is an easy flow of interactions and the environment really encourages interdisciplinary science.”
Original Article: Could tiny devices made out of DNA treat cancer?
More from: University of Chicago
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Mehrauli murder: Blood samples of victim’s father, brother collected for DNA analysis
“To ascertain that the bones belong to the victim, the blood samples of the father and brother of ‘A’ (Walkar) have been collected for DNA analysis. To find out if any incriminating evidence resides ...
- Black Friday 2022 live blog: Today's best Black Friday deals on top gifts this Christmas, toys, PS5 restocks, free money offers and more
The device boasts a 12 MP wide-angle back camera that supports ... One featured Chewy Black Friday deal worth checking out: You can save $60 on an Embark dog home DNA test. Learn more about your ...
- NIST in Joint Research Project with Korean Lab to Explore Medical Use of Shape-Memory Polymers
The joint research is expected to produce a DNA database of SMPs and foster development of SMPs for implantable devices that reduce the formation of biofilms caused by microbial infection. Established ...
- Out on a Limb: DNA test can be gift that keeps on giving
That’s because all DNA testing does is give you a good likelihood that you had ancestors at some point in the area marked by circles or colors or numbers or whatever other marking device the ...
- 'DNA' in plastic pollution can be used to hold manufacturers responsible for its clean-up
There's now an emerging area of technology that makes it possible to embed a traceable code, which researchers have likened to plastic "DNA", into plastic polymer ... that can be read on small ...
Go deeper with Google Headlines on:
[google_news title=”” keyword=”DNA device” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
Go deeper with Bing News on:
- DNA is providing new clues to why COVID-19 hits people differently
A massive international study examining DNA from more than 28,000 COVID-19 patients and almost 600,000 people who hadn’t been infected (to the best of their knowledge) confirmed that inheritance ...
- How a DNA "detective" helped solve an "unsolvable" Michigan cold case in four days
Detectives say Roxanne Wood had been sexually assaulted and her throat slashed. DNA was preserved from the crime scene, but given technological limitations of the time, there wasn't enough ...
- Always wanted an ancestry test? 23andMe DNA kits are on sale for up to 50% off.
Share on Facebook (opens in a new window) Share on Twitter (opens in a new window) Share on Flipboard (opens in a new window) All products featured here are independently selected by our editors ...
- Genetic genealogist helps solve a case that had "a gnat's eyebrow of DNA" left from the crime scene
Investigators found DNA at the crime scene and a sample was preserved. But given the limitations of technology in 1987, not much could be done with it. Terry continued to live under a cloud of ...
- MAC protein complex is essential for plants to protect themselves from DNA damage
In animals, DNA damage could lead to cancers. Although plants live for a long time without cancers, their growth is always challenged by many environmental factors, such as radiation, salinity ...
Go deeper with Google Headlines on:
[google_news title=”” keyword=”DNA nanodevices” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]