AI News, Cancer-fighting nanorobots programmed to seek and destroy tumors

Cancer-fighting nanorobots programmed to seek and destroy tumors

'We have developed the first fully autonomous, DNA robotic system for a very precise drug design and targeted cancer therapy,' said Hao Yan, director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics and the Milton Glick Professor in the School of Molecular Sciences.

The bricks to build their structures come from DNA, which can self-fold into all sorts of shapes and sizes -- all at a scale one thousand times smaller than the width of a human hair -- in the hopes of one day revolutionizing computing, electronics and medicine.

Nanomedicine is a new branch of medicine that seeks to combine the promise of nanotechnology to open up entirely new avenues for treatments, such as making minuscule, molecule-sized nanoparticles to diagnose and treat difficult diseases, especially cancer.

Until now, the challenge to advancing nanomedicine has been difficult because scientists wanted to design, build and carefully control nanorobots to actively seek and destroy cancerous tumors -- while not harming any healthy cells.

The NCNST researchers first wanted to specifically cut-off of tumor blood supply by inducing blood coagulation with high therapeutic efficacy and safety profiles in multiple solid tumors using DNA-based nanocarriers.

Nanorobots to the rescue To perform their study, the scientists took advantage of a well-known mouse tumor model, where human cancer cells are injected into a mouse to induce aggressive tumor growth.

Thrombin can block tumor blood flow by clotting the blood within the vessels that feed tumor growth, causing a sort of tumor mini-heart attack, and leading to tumor tissue death.

Once bound to the tumor blood vessel surface, the nanorobot was programmed, like the notorious Trojan horse, to deliver its unsuspecting drug cargo in the very heart of the tumor, exposing an enzyme called thrombin that is key to blood clotting.

'The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs, showing no detectable changes in normal blood coagulation or cell morphology,' said Yuliang Zhao, also a professor at NCNST and lead scientist of the international collaborative team.

ASU Now: Access, Excellence, Impact

For the past few decades, some scientists have known the shape of things to come in nanotechnology is tied to the molecule of life, DNA.

Similarly, DNA origami scientists are dreaming up a variety of shapes — at a scale one thousand times smaller than a human hair — that they hope will one day revolutionize computing, electronics and medicine.

Dubbed “single-stranded origami” (ssOrigami), their new strategy uses one long noodle-like strand of DNA, or its chemical cousin RNA, that can self-fold — without even a single knot — into the largest, most complex structures to date.

And the strands forming these structures can be made inside living cells or using enzymes in a test tube, allowing scientists the potential to plug-and-play with new designs and functions for nanomedicine: picture tiny nanobots playing doctor and delivering drugs within cells at the site of injury.

As proof of concept, they’ve pushed the envelope to make 18 shapes, including emoji-like smiley faces, hearts and triangles, that significantly expand the design studio space and material scalability for so-called, “bottom-up” nanotechnology.

“With help from a computer scientist in the team, we could also codify the design process as a mathematically rigorous formal algorithm and automate the design by developing a user-friendly software tool.” The algorithm and software were validated by the automated design and experimental construction of six distinct DNA ssOrigami structures (four rhombuses and two heart shapes).

“We are actively looking at the first nanomedicine applications with our ssOrigami technology.” They were also able to demonstrate that a folded ssOrigami structure can be melted and used as a template for amplification by DNA copying enzymes in a test tube and that the ssOrigami strand can be replicated and amplified via clonal production in living cells.

“Single-stranded DNA nanostructures formed via self-folding offer greater potential of being amplifiable, replicable and clonable, and hence the opportunity for cost-efficient, large-scale production using enzymatic and biological replication, as well as the possibility for using in-vitro evolution to produce sophisticated phenotypes and functionalities,” Yan said.

“The ideal situation would be to design an RNA sequence that can get transcribed inside the bacteria, and fold inside the bacteria so we can use bacteria as a nanofactory to produce the material.” In the software made through a collaboration with BioNano Research Group, Autodesk Research, the user selects a target shape, which is converted into pixelated representation.

DNA Robots Target Cancer

BAOQUAN DING AND HAO YANDNA nanorobots that travel the bloodstream, find tumors, and dispense a protein that causes blood clotting trigger the death of cancer cells in mice, according to a study published today (February 12) in Nature Biotechnology.

The authors have “demonstrated that it’s indeed possible to do site-specific drug delivery using biocompatible, biodegradable, DNA-based bionanorobots for cancer therapeutics,”

The authors designed the fasteners to dissociate when they bind nucleolin—a protein specific to the surface of tumor blood-vessel cells—at which point, the tube opens and exposes its cargo.Nanorobot design.

Yan’s team also found that nanorobot treatment increased survival and led to smaller tumors in a mouse model of melanoma, and in mice with xenografts of human ovarian cancer cells.

The next step is to investigate any damage—such as undetected clots or immune-system responses—in the host organism, he says, as well as to determine how much thrombin is actually delivered at the tumor sites.

The authors showed in the study that the nanorobots didn’t cause clotting in major tissues in miniature pigs, which satisfies some safety concerns, but Yan agrees that more work is needed.

Cancer-hunting 'nanorobots' able to shrink tumours by cutting off blood supply

Nanometre-sized “robots” have successfully been used for the first time in mammals to deliver drugs to specific places to treattumours.

Starved of their blood supply, tumours began to shrink and the cancer’s ability to spread and grow in new sites also appeared to be reduced,doubling the life expectancyor removing tumours entirelyinsome mouse cancers.

This demonstration, which marks a major step towards the implementation of nanobot drug delivery in medicine, could pave the way for delivering toxic chemotherapy drugs with reduced side effects, among a host of other uses.

The international team, including researchers from China, Australia and the US, primed their nanobots to release in the presence of the protein molecule, nucleolin, which coats the internal walls of blood vessels feeding tumours.

Within 24 hours of the treatment the scientists saw blood vessels feeding the primary tumour site had been cut off, with solid clots forming in all tumour blood vessels over the next 72 hours – causing the tumour to start to die.

The treatment was most effective in treating mice with melanoma cancers, which have a very strong blood supply, where three out of the eight mice treated showed complete regression of their tumours.

“Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumours and vascularized metastases”.

Programmable DNA Nanorobots Shrink Tumors by Blocking Their Blood Supply

A team of scientists in the U.S. and China has created programmable DNA origami nanorobots that can seek out and shrink tumors by blocking their blood supply.

Tests in mice carrying breast, melanoma, ovarian, and lung tumors showed how the DNA nanorobots homed in on cancer-feeding blood vessels and induced the formation of clots, which effectively shut off the tumors' lifeline of oxygen and nutrients.

To achieve this, Hao Yan’s team turned to DNA origami as the foundation for developing a DNA nanorobot system, based on a self-assembled nanotube, which could deliver the coagulation protease thrombin specifically to tumors and essentially cause thrombosis in tumor-feeding blood vessels, but without affecting vasculature in healthy tissues.

The tube structure is held together by fastener strands that include DNA aptamer molecules designed to nucleolin, a protein specifically expressed on tumor-associated endothelial cells.

The scientists hypothesized that the aptamer molecules on the DNA nanorobots would recognize and bind to their nucleolin targets on tumor blood vessels, triggering the fastening strips to pop open.

The nanorobot therapy was particularly effective in a melanoma mouse model, in which three of eight treated mice showed complete tumor regression and more than double median survival time.

The nanorobot therapy also effectively prevented the development of melanoma metastases in the liver, “which can likely be attributed to the inhibition of primary tumor progression or to the regression of vascularized metastases,”

"The nanorobot proved to be safe and immunologically inert for use in normal mice and also in Bama miniature pigs, showing no detectable changes in normal blood coagulation or cell morphology,"

"Treatment with [the] nanorobot-Th system did not lead to any significant variations in the blood coagulation parameters or histological morphology when compared to the control group, demonstrating that the nanorobot-Th is decidedly safe in the normal tissues of large animals,”

“DNA nanorobotic systems, such as the one we describe here with targeting and triggered release properties, may inspire the design of novel cancer therapeutics modified with different targeting ligands to mediate delivery of multiple biologically active payloads, such as short interfering RNA (siRNA), chemotherapeutics or peptide drugs,”

"Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumors and vascularized metastases.

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