Could tiny devices made out of DNA treat cancer?

One of the most promising ways to treat cancer is to restore our immune system. 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 regression of tumors.

The problem with drug delivery is that it is delivery, delivery, and delivery, explained Yamuna Krishnan, a professor in the Department of Chemistry and an author of the study.

The focus of these devices is on a particular type of cell. If something goes wrong with the macrophages, they can become a key part of the cancer. Up to 50% of breast cancer's mass can be found in triple-negative breast cancer.

Lev Becker, an associate professor in the Ben May Department for Cancer Research, said that mechanisms underlying their impact on tumor development and therapeutic strategies to target them are not understood.

The immune system recognizes cancer cells through the use of TAMs. There is a subpopulation of immune cells called CD8+ T cells that are critical in recognizing and killing cancer cells. CD8+ T cells can be activated by binding to antigens on the surface of cancer cells. The strategy goes awry when there is nothing for the T-cells to recognize.

The group of Becker found that there was a high level of cysteine proteases in TAMs. They knew that these particular enzymes live in lysosomes, which work as the "stomach" of the cell, so Becker thought that they might be over-digesting tumors.

To test this idea, Becker's group needed to prove that the problem really was in the lysosomes eating away at the antigens. They used mice that lacked aProtein that regulates lysosomal enzyme levels and activity. They found that the lysosomes in the mice weren't destroying as much. This allowed CD8+ T cells to attack the tumor.

They needed to figure out a way to target the process.

Krishnan had developed the ability to send tiny devices made out of DNA directly to the lysosomes of specific immune cells in model organisms. The two labs worked together to overcome the challenge.

A former graduate student of the Krishnan lab and now a researcher in Becker's lab has developed a tiny DNA device that can deliver a cysteine protease inhibitor. When Chang Cui, a graduate student in the Becker lab, injected it into a mouse with a tumor, it preferentially targeted lysosomes inside the tumors, where it stopped the enzymes from destroying the antigens.

In tests with mice, a triple-negative-breast-cancer model was regression in tests with this DNA device. This type of cancer is difficult to treat and this outcome was exciting.

It is a fundamentally different approach from the standard way that researchers think about treating cancer. Natural immunity takes care of the rest when the switch is flipped in a TAM.

The researchers hope that this new delivery method is the next generation of drug targeting.

The scientists said that it could go beyond cancer, because it could impact a broad range of diseases where immunity has gone awry.

The chemistry and biologists are in the same building, so there is an easy flow of interactions.

More information: Chang Cui et al, A lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumours, Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-00988-z Journal information: Nature Nanotechnology Citation: Could tiny devices made out of DNA treat cancer? (2022, March 3) retrieved 3 March 2022 from https://phys.org/news/2022-03-tiny-devices-dna-cancer.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.