These Nanorobots Kill Cancer Cells Without Harming Healthy Tissue

Researchers in Sweden have developed DNA-based nanorobots that can trigger the death of cancer cells by detecting the acidic environment surrounding solid tumours, offering a potential new approach to cancer treatment that could reduce damage to healthy tissue.

The technology, developed by scientists at Karolinska Institutet in Stockholm, uses a molecular structure that conceals a cell-killing mechanism until it encounters conditions commonly found around tumours. In experiments involving mice with human breast cancer tumours, the nanodevice reduced tumour growth by up to 70% compared with an inactive version, according to research published in the journal Nature Nanotechnology in July 2024.

The findings highlight the potential of nanomedicine, which uses materials and devices engineered at the nanometre scale to deliver treatments, detect disease or interact with biological systems. But the Swedish technology remains at the preclinical research stage and has not been established as a safe or effective treatment for people.

Cancer killed an estimated 9.7 million people worldwide in 2022, while about 20 million new cases were diagnosed, according to the World Health Organization’s International Agency for Research on Cancer. The agency projects that annual new cases could reach 35 million by 2050, a 77% increase from 2022, driven largely by population growth, ageing and other demographic changes.

HOW THE NANOROBOTS WORK

The technology relies on a technique called DNA origami, in which researchers fold DNA molecules into predetermined nanoscale shapes that can hold and arrange other biological molecules with high precision.

The Swedish research team, led by Professor Björn Högberg at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics, built a nanostructure that conceals six short amino-acid chains, known as peptides, in a hexagonal arrangement.

When exposed to the more acidic conditions commonly found in the microenvironment surrounding solid tumours, the structure changes to expose the peptides. These bind to death receptors on the surface of cancer cells, clustering the receptors and activating apoptosis, the programmed process by which cells die.

“This hexagonal nanopattern of peptides becomes a lethal weapon,” Högberg said in a statement released by Karolinska Institutet.

“If you were to administer it as a drug, it would indiscriminately start killing cells in the body, which would not be good. To get around this problem, we have hidden the weapon inside a nanostructure built from DNA.”

The researchers designed the device to remain inactive under normal physiological conditions. In laboratory experiments, the peptide arrangement remained concealed at a pH of 7.4, close to that of normal blood, but became active at pH 6.5, a more acidic condition associated with the tumour microenvironment. The study found that the switch could activate the cell-killing mechanism in human breast cancer cells under the more acidic conditions.

This conditional activation is central to the approach. Conventional cancer treatments can affect healthy cells as well as malignant ones, depending on the therapy and its distribution throughout the body. A molecular device that activates its toxic mechanism preferentially around a tumour could, in principle, improve treatment selectivity.

The nanorobot does not navigate through the body like a miniature mechanical machine. Instead, it is a programmable molecular structure designed to respond autonomously to a chemical signal in its surroundings.

WHAT THE MOUSE EXPERIMENTS SHOWED

The researchers tested the device in mice carrying human breast cancer xenografts, in which human tumour cells are implanted into animals. The treatment reduced tumour growth by up to 70% compared with an inactive version of the nanostructure, the study reported.

The result provides evidence that the molecular switch can function in a living organism, moving the concept beyond experiments conducted exclusively in laboratory cell cultures.

However, a reduction in tumour growth in mice does not demonstrate that the technology can eliminate cancer, extend survival or improve outcomes in human patients. Nor does it establish whether the treatment would work across different tumour types, stages of disease or biological environments.

The researchers said further testing was needed to establish the technology’s effectiveness and safety.

“We now need to investigate whether this works in more advanced cancer models that more closely resemble the real human disease,” said Yang Wang, the study’s first author and a researcher at Karolinska Institutet.

“We also need to find out what side effects the method has before it can be tested on humans.”

The distinction is important because the receptors targeted by the nanorobot are also present on healthy cells. Although the device is designed to conceal its active component under normal conditions, researchers must establish whether it can avoid unintended activation and damage in healthy tissues.

THE CHALLENGE OF TARGETED CANCER TREATMENT

The Swedish research addresses a longstanding problem in oncology: how to destroy malignant cells while limiting harm to surrounding tissue.

Chemotherapy can circulate throughout the body, exposing healthy cells to drugs designed to kill rapidly dividing cancer cells. Radiation therapy can damage healthy tissue near a tumour, although modern techniques aim to concentrate radiation on the target. Other treatments, including targeted therapies and immunotherapies, use different mechanisms to attack cancer, with effectiveness and side effects varying by disease and patient.

Nanomedicine seeks to improve treatment delivery and selectivity by engineering materials that interact with particular biological features. Some systems are designed to transport drugs to tumours, while others respond to local conditions such as acidity, temperature or specific molecular markers.

DNA origami offers researchers a way to position biological molecules at precisely defined distances and orientations. In the Swedish study, the hexagonal arrangement is important because it brings death-receptor-binding peptides together in a pattern that can trigger the cell’s programmed death mechanism.

The researchers’ work therefore involves more than packaging a conventional drug inside a tiny carrier. It attempts to control when a biological mechanism becomes active by engineering the structure of the treatment itself.

The team also identified further opportunities to improve targeting, including attaching proteins or peptides to the nanorobot’s surface that bind to particular cancer types. Such modifications could help direct the device towards selected tumours, although their effectiveness remains to be established.

FROM LABORATORY RESEARCH TO CLINICAL USE

The path from a promising animal experiment to an approved cancer treatment is long. Researchers would need to determine how the nanostructures behave after administration, whether they reach tumours in sufficient quantities, how long they remain in the body and how they are broken down or eliminated.

They would also need to investigate immune responses, toxicity, unintended activation and whether the acidic conditions surrounding different tumours are sufficiently consistent to produce reliable results.

Tumours vary in their biology, blood supply, acidity and response to treatment. A mechanism that works against one experimental breast cancer model may not produce the same effect in other cancers or in patients whose tumours have developed resistance to treatment.

Human clinical trials would ultimately be needed to establish safety, appropriate dosing and effectiveness. The 2024 study did not establish a timeline for clinical availability.

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