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Mount Sinai Researchers Create a “Smart Tweezer” That Can Isolate a Single Bacterium from a Microbiome Sample Prior to Genetic Sequencing

New technology could enable genetic scientists to identify antibiotic resistant genes and help physicians choose better treatments for genetic diseases

Genomic scientists at the Icahn School of Medicine at Mount Sinai Medical Center in New York City have developed what they call a “smart tweezer” that enables researchers to isolate a single bacterium from a patient’s microbiome in preparation for genetic sequencing. Though primarily intended for research purposes, the new technology could someday be used by clinical laboratories and microbiologists to help physicians diagnose chronic disease and choose appropriate genetic therapies.

The researchers designed their new technology—called mEnrich-seq—to improve the effectiveness of research into the complex communities of microorganisms that reside in the microbiomes within the human body. The discovery “ushers in a new era of precision in microbiome research,” according to a Mount Sinai Hospital press release.

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that sequences specific bacterial taxa of interest, but not most background taxa. We developed mEnrich-seq (in which ‘m’ stands for methylation and seq for sequencing) for enriching taxa of interest from metagenomic DNA before sequencing,” the scientists wrote in a paper they published in Nature Methods titled, “mEnrich-seq: Methylation-Guided Enrichment Sequencing of Bacterial Taxa of Interest from Microbiome.”

“Imagine you’re a scientist who needs to study one particular type of bacteria in a complex environment. It’s like trying to find a needle in a large haystack,” said the study’s senior author Gang Fang, PhD (above), Professor of Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai Medical Center, in a press release. “mEnrich-seq essentially gives researchers a ‘smart tweezer’ to pick up the needle they’re interested in,” he added. Might smart tweezers one day be used to help physicians and clinical laboratories diagnose and treat genetic diseases? (Photo copyright: Icahn School of Medicine.)

Addressing a Technology Gap in Genetic Research

Any imbalance or decrease in the variety of the body’s microorganisms can lead to an increased risk of illness and disease.

“Imbalance of the normal gut microbiota, for example, have been linked with conditions including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), obesity, type 2 diabetes, and allergies. Meanwhile, the vaginal microbiome seems to impact sexual and reproductive health,” Inside Precision Medicine noted.

In researching the microbiome, many scientists “focus on studying specific types of bacteria within a sample, rather than looking at each type of bacteria present,” the press release states. The limitation of this method is that a specific bacterium is just one part of a complicated environment that includes other bacteria, viruses, fungi and host cells, each with their own unique DNA.

“mEnrich-seq effectively distinguishes bacteria of interest from the vast background by exploiting the ‘secret codes’ written on bacterial DNA that bacteria use naturally to differentiate among each other as part of their native immune systems,” the press release notes. “This new strategy addresses a critical technology gap, as previously researchers would need to isolate specific bacterial strains from a given sample using culture media that selectively grow the specific bacterium—a time-consuming process that works for some bacteria, but not others. mEnrich-seq, in contrast, can directly recover the genome(s) of bacteria of interest from the microbiome sample without culturing.”

Isolating Hard to Culture Bacteria

To conduct their study, the Icahn researchers used mEnrich-seq to analyze urine samples taken from three patients with urinary tract infections (UTIs) to reconstruct Escherichia coli (E. Coli) genomes. They discovered their “smart tweezer” covered more than 99.97% of the genomes across all samples. This facilitated a comprehensive examination of antibiotic-resistant genes in each genome. They found mEnrich-seq had better sensitivity than standard study methods of the urine microbiome. 

They also used mEnrich-seq to selectively examine the genomes of Akkermansia muciniphila (A. muciniphila), a bacterium that colonizes the intestinal tract and has been shown to have benefits for obesity and Type 2 diabetes as well as a response to cancer immunotherapies.

Akkermansia is very hard to culture,” Fang told GenomeWeb. “It would take weeks for you to culture it, and you need special equipment, special expertise. It’s very tedious.”

mEnrich-seq was able to quickly segregate it from more than 99.7% of A. muciniphila genomes in the samples.

Combatting Antibiotic Resistance Worldwide

According to the press release, mEnrich-seq could potentially be beneficial to future microbiome research due to:

  • Cost-Effectiveness: It offers a more economical approach to microbiome research, particularly beneficial in large-scale studies where resources may be limited.
  • Broad Applicability: The method can focus on a wide range of bacteria, making it a versatile tool for both research and clinical applications.
  • Medical Breakthroughs: By enabling more targeted research, mEnrich-seq could accelerate the development of new diagnostic tools and treatments.

“One of the most exciting aspects of mEnrich-seq is its potential to uncover previously missed details, like antibiotic resistance genes that traditional sequencing methods couldn’t detect due to a lack of sensitivity,” Fang said in the news release. “This could be a significant step forward in combating the global issue of antibiotic resistance.”

More research and clinical trials are needed before mEnrich-seq can be used in the medical field. The Icahn researchers plan to refine their novel genetic tool to improve its efficiency and broaden its range of applications. They also intend to collaborate with physicians and other healthcare professionals to validate how it could be used in clinical environments.  

Should all this come to pass, hospital infection control teams, clinical laboratories, and microbiology labs would welcome a technology that would improve their ability to detect details—such as antibiotic resistant genes—that enable a faster and more accurate diagnosis of a patient’s infection. In turn, that could contribute to better patient outcomes.

—JP Schlingman

Related Information:

‘Smart Tweezer’ Can Pluck Out Single Bacterium Target from Microbiome

mEnrich-seq: Methylation-guided Enrichment Sequencing of Bacterial Taxa of Interest from Microbiome

Genomic ‘Tweezer’ Ushers in a New Era of Precision in Microbiome Research

Molecular Tweezers Can Precisely Select Microbiome Bacteria

Identification of DNA Motifs that Regulate DNA Methylation

New Bacterial Epigenetic Sequencing Method Could Be Boon for Complex Microbiome Analyses

Former FDA Director to Speak at Executive War College on FDA’s Coming Regulation of Laboratory Developed Tests

Tim Stenzel, MD, PhD, will discuss what clinical laboratories need to know about the draft LDT rule, FDA memo on assay reclassification, and ISO-13485 harmonization

Many clinical laboratories anxiously await a final rule from the US Food and Drug Administration (FDA) that is expected to establish federal policies under which the agency will regulate laboratory developed tests (LDTs). The agency released a proposed rule on Oct. 3, 2023, setting a Dec. 4 deadline for submission of comments. The White House’s Office of Management and Budget received a draft of the final rule less than three months later on March 1, 2024.

“Given how fast it moved through HHS, the final [rule] is likely pretty close” to the draft version, wrote former FDA commissioner Scott Gottlieb, MD, in a post on LinkedIn. Gottlieb and other regulatory experts expect the White House to submit the final rule to Congress no later than May 22, and perhaps as soon as this month.

But what will the final rule look like? Tim Stenzel, MD, PhD, former director of the FDA’s Office of In Vitro Diagnostics, suggests that it is too soon to tell.

Stenzel, who retired from the FDA last year, emphasized that he was not speaking on behalf of the federal agency and that he adheres to all FDA confidentiality requirements. He formed a new company—Grey Haven LLC—through which he is accepting speaking engagements in what he describes as a public service.

“I’m taking a wait and see approach,” said Tim Stenzel, MD, PhD (above), former director of the FDA’s Office of In Vitro Diagnostics, in an interview with Dark Daily. “The rule is not finalized. The FDA received thousands of comments. It’s my impression that the FDA takes those comments seriously. Until the rule is published, we don’t know what it will say, so I don’t think it does any good to make assumptions.” Clinical laboratory leaders will have an opportunity to learn how to prepare for FDA regulation of LDTs directly from Stenzel at the upcoming Executive War College in May. (Photo copyright: LinkedIn.)

FDA’s History of LDT Regulation

Prior to his five-year stint at the agency, Stenzel held high-level positions at diagnostics manufacturers Invivoscribe, Quidel Corporation, Asuragen, and Abbott Laboratories. He also directed the clinical molecular diagnostics laboratory at Duke University Medical Center in North Carolina. In the latter role, during the late 1990s, he oversaw development of numerous LDTs, he said.

The FDA, he observed, has long taken the position that it has authority to regulate LDTs. However, since the 1970s, after Congress passed the Medical Device Amendments to the federal Food, Drug, and Cosmetic Act, the agency has generally exercised “enforcement discretion,” he said, in which it declined to regulate most of these tests.

At the time, “many LDTs were lower risk, small volume, and used for specialized needs of a local patient population,” the agency stated in a press release announcing the proposed rule. “Since then, due to changes in business practices and increasing ability to ship patient specimens across the country quickly, many LDTs are now used more widely, for a larger and more diverse population, with large laboratories accepting specimens from across the country.”

Clinical Labs Need a Plan for Submission of LDTs to FDA

The FDA proposed the new rule after Congress failed to vote on the VALID Act (Verifying Accurate Leading-edge IVCT Development Act of 2021), which would have established a statutory framework for FDA oversight of LDTs. Citing public comments from FDA officials, Stenzel believes the agency would have preferred the legislative approach. But when that failed, “they thought they needed to act, which left them with the rulemaking path,” he said.

The new rule, as proposed, would phase out enforcement discretion in five stages over four years, he noted. Labs would have to begin submitting high-risk tests for premarket review about three-and-a-half years from publication of the final rule, but not before Oct. 1, 2027. Premarket review requirements for moderate- or low-risk tests would follow about six months later.

While he suggested a “wait and see” approach to the final rule, he advises labs that might be affected to develop a plan for dealing with it.

Potential Lawsuits

Stenzel also noted the likelihood of litigation in which labs or other stakeholders will seek to block implementation of the rule. “It’s a fairly widespread belief that there will be a lawsuit or lawsuits that will take this issue through the courts,” he said. “That could take several years. There is no guarantee that the courts will ultimately side with the FDA.”

In “Perfect Storm of Clinical Lab and Pathology Practice Regulatory Changes to Be Featured in Discussions at 29th Annual Executive War College,” Dark Daily covers how the forces in play will directly impact the operations and financial stability of many of the nation’s clinical laboratories.

Stenzel is scheduled to speak about the LDT rule during three sessions at the upcoming Executive War College on Diagnostic, Clinical Laboratory, and Pathology Management conference taking place on April 30-May 1 in New Orleans.

He acknowledged that it is a controversial issue among clinical laboratories. Many labs have voiced opposition to the rule as well as the Valid Act.

Currently in retirement, Stenzel says he is making himself available as a resource through public speaking for laboratory professionals and other test developers who are seeking insights about the agency.

“The potential value that I bring is recent experience with the FDA and with stakeholders both inside and outside the FDA,” he said, adding that during his presentations he likes “to leave plenty of time for open-ended questions.”

In the case of his talks at the Executive War College, Stenzel said he anticipates “a robust conversation.”

He also expects to address other FDA-related issues, including:

  • A recent memo in which the agency said it would begin reclassifying most high-risk In Vitro Diagnostic (IVD) tests—those in class III (high risk)—into class II (moderate to high risk).
  • The emergence of multi-cancer detection (MCD) tests, which he described as a “hot topic in the LDT world.” The FDA has not yet approved any MCD tests, but some are available as LDTs.
  • A new voluntary pilot program in which the FDA will evaluate LDTs in situations where the agency has approved a treatment but has not authorized a corresponding companion diagnostic.
  • An FDA effort to harmonize ISO 13485—a set of international standards governing development of medical devices and diagnostics—with the agency’s own quality system regulations. Compliance with the ISO standards is necessary to market products in many countries outside the US, particularly in Europe, Stenzel noted. Harmonization will simplify product development, he said, because manufacturers won’t have to follow two or more sets of rules.

To learn how to prepare for the FDA’s future regulation of LDTs, clinical laboratory and pathology group managers would be wise to attend Stenzel’s presentations at this year’s Executive War College. Visit here to learn more and to secure your seat in New Orleans.

—Stephen Beale

Related Information:

FDA Proposes Rule Aimed at Helping to Ensure Safety and Effectiveness of Laboratory Developed Tests

Proposed Rule Webinar: Medical Devices; Laboratory Developed Tests (webinar transcript)

Proposed Rule Webinar: Medical Devices; Laboratory Developed Tests (slides)

FDA Proposed Rule on Medical Devices; Laboratory Developed Tests

CDRH Announces Intent to Initiate the Reclassification Process for Most High Risk IVDs

Questions and Answers about Multi-Cancer Detection Tests Oncology Drug Products Used with Certain In Vitro Diagnostics Pilot Program

Swiss Research Study into Long COVID Promises New Diagnostic and Therapeutic Possibilities

New biomarker may lead to new clinical laboratory testing and treatments for long COVID

Researchers studying long COVID at the University Hospital of Zurich (UZH) and the Swiss Institute of Bioinformatics (SIB), both in Switzerland, have discovered a protein biomarker in blood that indicates a component of the body’s innate immune system—called the complement system—remains active in some individuals long after the infection has run its course. The scientists are hopeful that further studies may provide clinical laboratories with a definitive test for long COVID, and pharma companies with a path to develop therapeutic drugs to treat it.

Ever since the COVID-19 pandemic began, a subset of the population worldwide continues to experience lingering symptoms even after the acute phase of the illness has passed. Patients with long COVID experience symptoms for weeks, even months after the initial viral infection has subsided. And because these symptoms can resemble other illnesses, long COVID is difficult to diagnose. 

This new biomarker may lead to new clinical laboratory diagnostic blood tests for long COVID, and to a greater understanding of why long COVID affects some patients and not others.

The Swiss scientists published their findings in the journal Science titled, “Persistent Complement Dysregulation with Signs of Thromboinflammation in Active Long COVID.”

“Those long COVID patients used to be like you and me, totally integrated [into] society with a job, social life, and private life,” infectious disease specialist Michelè van Vugt, MD (above), Senior Fellow and Professor at Amsterdam Institute for Global Health and Development (AIGHD), told Medical News Today. “After their COVID infection, for some of them, nothing was left because of their extreme fatigue. And this happened not only in one patient but many more—too many for only [a] psychological cause.” Clinical laboratories continue to perform tests on patients experiencing symptoms of COVID-19 even after the acute illness has passed. (Photo copyright: AIGHD.)

Role of the Complement System

To complete their study, the Swiss scientists monitored 113 patients who were confirmed through a reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test to have COVID-19. The study also included 39 healthy control patients who were not infected.

The researchers examined 6,596 proteins in 268 blood samples collected when the sick patients were at an acute stage of the virus, and then again six months after the infection. They found that 40 of the patients who were sick with COVID-19 eventually developed symptoms of long COVID. Those 40 patients all had a group of proteins in their blood showing that the complement system of their immune system was still elevated even after recovering from the virus.

“Complement is an arm of the immune system that ‘complements’ the action of the other arms,” Amesh Adalja, MD, Adjunct Assistant Professor at Johns Hopkins Bloomberg School of Public Health, told Prevention, “Activities that it performs range from literally attacking the cell membranes of a pathogen to summoning the cells of other immune systems to the site of infection.”

In addition to helping bodies heal from injury and illness, the complement immune system also activates inflammation in the body—and if the complement system is activated for too long the patient is at risk for autoimmune disease and other inflammatory conditions.

This inflammation may cause microclots in patients. “These can block the blood vessels and lead to damage … That can cause premature cardiac events, dementia, respiratory failure, and renal failure,” infectious disease specialist Thomas Russo, MD, SUNY Distinguished Professor, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, told Prevention.

Brain Fog

To make matters worse for long COVID patients, a recent study published in Nature Neuroscience titled, “Blood-Brain Barrier Disruption and Sustained Systemic Inflammation in Individuals with Long COVID-Associated Cognitive Impairment,” found that nearly 50% of people who experience long COVID also experience a condition called Brain Fog (aka, mental fog or clouding of consciousness.)

Conducted by genetic scientists at Trinity College Dublin and St. James’ Hospital in Dublin, Ireland, the study “analyzed blood samples—specifically, serum and plasma—from 76 patients who were hospitalized with COVID-19 in March or April 2020, along with those from 25 people taken before the pandemic. The researchers discovered that people who said they had brain fog had higher levels of a protein in their blood called S100β [a calcium-binding protein] than people who didn’t have brain fog,” Prevention reported.

“S100β is made by cells in the brain and isn’t normally found in the blood. That suggests that the patients had a breakdown in the blood-brain barrier, which blocks certain substances from getting to the brain and spinal cord, the researchers noted,” Prevention reported.

“The scientists then did MRI scans with dye of 22 people with long COVID (11 of them who reported having brain fog), along with 10 people who recovered from COVID-19. They found that long COVID patients who had brain fog had signs of a leaky blood-brain barrier,” Prevention noted.

“This leakiness likely disrupts the integrity of neurons in the brain by shifting the delicate balance of materials moving into and out of the brain,” Matthew Campbell, PhD, Professor and Head of Genetics at Trinity College Dublin, told Prevention.

Interactions with Other Viruses

According to Medical News Today, the Swiss study results also suggest that long COVID symptoms could appear because of the reactivation of a previous herpesvirus infection. The patients in the study showed increased antibodies against cytomegalovirus, a virus that half of all Americans have contracted by age 40.

The link between long COVID and these other viruses could be key to developing treatment for those suffering with both illnesses. The antiviral treatments used for the herpesvirus could potentially help treat long COVID symptoms as well, according to Medical News Today.

“Millions of people across the planet have long COVID or will develop it,” Thomas Russo MD, Professor and Chief of Infectious Disease at the University at Buffalo in New York, told Prevention. “It’s going to be the next major phase of this pandemic. If we don’t learn to diagnose and manage this, we are going to have many people with complications that impact their lives for the long term.”

Long COVID won’t be going away any time soon, much like the COVID-19 coronavirus. But these two studies may lead to more effective clinical laboratory testing, diagnoses, and treatments for millions of people suffering from the debilitating condition.

—Ashley Croce

Related Information:

New Study Finds Potential Cause of Long COVID Symptoms—Experts Explain

Persistent Complement Dysregulation with Signs of Thromboinflammation in Active Long COVID

CDC: Long COVID or Post-COVID Conditions

Long COVID: Major Findings, Mechanisms and Recommendations

Long COVID Explanation in New Study Possibly Paves Way for Tests and Treatments

Scientists May Have Discovered Reason for Long COVID Brain Fog—Here’s Why It Matters

Blood–Brain Barrier Disruption and Sustained Systemic Inflammation in Individuals with Long COVID-Associated Cognitive Impairment

Could New Clues on How Long COVID Affects Immune System Lead to Treatment?

Scientists at UT Health San Antonio Discover New Biomarker for Diabetic Kidney Disease

Biomarker may lead to clinical laboratory testing that enables clinical pathologists and urologists to diagnose risk for diabetic kidney failure years before it occurs

Clinical laboratories working with nephrologists and urologists to diagnose patients experiencing urinary system difficulties know that albumin (excessive protein found in the urine) is a common biomarker used in clinical laboratory testing for kidney disease. But patients with diabetes generally have low protein in their urine due to that disease. Thus, it is difficult to diagnose early stage kidney failure in diabetic patients.

But now, researchers at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered a biomarker called adenine (also found in the urine) which, they say, offers the ability to diagnose diabetic patients at risk of kidney failure significantly earlier than other biomarkers.

A UT Health San Antonio news release states, “Urine levels of adenine, a metabolite produced in the kidney, are predictive and a causative biomarker of looming progressive kidney failure in patients with diabetes, a finding that could lead to earlier diagnosis and intervention.”

The study’s senior author Kumar Sharma, MD, professor and Chief of Nephrology at UT Health San Antonio, said, “The finding paves the way for clinic testing to determine—five to 10 years before kidney failure—that a patient is at risk.”

The UT Health scientists published their research in the Journal of Clinical Investigation (JCI) titled, “Endogenous Adenine Mediates Kidney Injury in Diabetic Models and Predicts Diabetic Kidney Disease in Patients.”

“The study is remarkable as it could pave the way to precision medicine for diabetic kidney disease at an early stage of the disease,” said study lead Kumar Sharma, MD (above), professor and Chief of Nephrology at UT Health San Antonio, in a news release. This would be a boon to clinical laboratories and pathology groups that work with urologists to diagnose and treat diabetic patients who are at-risk for kidney failure. (Photo copyright: UT Health San Antonio.)

Completing the UT Health Study

Sharma and his team worked for five years to discover that the adenine molecule was damaging kidney tissue, News4SA reported. The research required the team to develop new methods for viewing small molecules known as metabolites.

“UT Health San Antonio is one of few centers in the US perfecting a technique called spatial metabolomics on kidney biopsies from human patients,” the news release notes. The kidney biopsies were obtained through the Kidney Precision Medicine Project (KPMP) and were gathered from various US academic centers.

“It’s a very difficult technique, and it took us several years to develop a method where we combine high resolution of the geography of the kidney with mass spectrometry analysis to look at the metabolites,” Sharma said.

Testing by the UT Health team unearthed “endogenous adenine around scarred blood vessels in the kidney and around tubular-shaped kidney cells that were being destroyed. Endogenous substances are those that naturally occur in the body,” the news release notes.

Findings Could Affect Diabetic Care

UT Health San Diego’s study findings could allow for early intervention and change the way diabetes care is managed, Sharma said.

“The study results are significant because until now, the most important marker for kidney disease has been protein (or albumin) in the urine. Up to half of diabetes patients who develop kidney failure never have much protein in their urine. As 90% of patients with diabetes (more than 37 million patients in the US) remain at increased risk despite low levels of albumin in their urine, this study has widespread consequences. It is the first study to identify these patients at an early stage by measuring this new causative marker in the urine,” the UT Health news release states.

“We’re hoping that by identifying patients early in their course, and with new therapies targeting adenine and kidney scarring, we can block kidney disease or extend the life of the kidney much longer,” Sharma said.

Getting Ahead of Kidney Disease

Though many patients recognize their risk for kidney disease, those who do not have protein in their urine may not take the risk seriously enough, Sharma noted.

“They could be feeling a false sense of security that there is no kidney disease occurring in their body, but in fact, in many cases it is progressing, and they often don’t find out until the kidney disease is pretty far advanced. And at that time, it is much harder to protect the kidneys and prevent dialysis,” he said in the new release.

“Once a patient needs dialysis, he or she must have a fistula or catheter placed and go on a dialysis machine three times a week, four hours at a time to clean the blood,” the news release states.

“The death rate is very high, especially in patients with diabetes,” Sharma added. “There is about 40% mortality within five years in patients with diabetes and kidney failure.”

Though measuring adenine in urine is a challenge, Sharma and his team developed a method that can be performed at UT Health San Antonio on at-risk patients with a doctor’s order. The test results go back to the patient’s doctor.

“The test is being approved for clinical use and right now it is an experimental test, but we expect it to be available for all patients in the near future.” Sharma told News4SA.

“What we’re hoping is that by identifying patients early in their course, and with new therapies targeting adenine and kidney scarring, we can block kidney disease or extend the life of the kidney much longer,” Sharma said in the news release.

And so, thanks to the UT Health researchers, pathologists and clinical laboratories may soon see a new diagnostic test biomarker that will help urologists identify diabetic patients at-risk for kidney failure years earlier than previously possible.

—Kristin Althea O’Connor

Related Information:

Endogenous Adenine Mediates Kidney Injury in Diabetic Models and Predicts Diabetic Kidney Disease in Patients

Metabolite in Urine Predicts Diabetic Kidney Failure 5-10 Years Early; Oral Therapeutic Drug Shows Promise in Mice

Revolutionizing Diabetes Care: UT Health San Antonio’s Breakthrough in Predicting Kidney Failure

UT Health San Antonio Discovers Molecule Predicting Kidney Failure in Diabetics

Rice University Researchers Develop ‘Molecular Jackhammer’ That Kills Cancer Cells

Research could lead to similar treatments for other diseases, as well as creating a demand for a new line of oncology tests for clinical labs and pathology groups

Cancer treatment has come a long way in the past decades, and it seems poised to take another leap forward thanks to research being conducted at Rice University in Houston. Molecular scientists there have developed what they call a “molecular jackhammer” that uses special molecules and near-infrared light to attack and kill cancer cells.

The technique has been effective in research settings. Should it be cleared for use in patient care, it could change the way doctors treat cancer patients while giving clinical laboratories a new diagnostic tool that could guide treatment decisions.      

The researchers “found that the atoms of a small dye molecule used for medical imaging can vibrate in unison—forming what is known as a plasmon [a quantum of plasma oscillation]—when stimulated by near-infrared light, causing the cell membrane of cancerous cells to rupture,” a Rice University news release noted.

The small dye molecule is called aminocyanine, a type of fluorescent synthetic dye that is already in use in medical imaging.

“These molecules are simple dyes that people have been using for a long time,” said physical chemistry scientist Ciceron Ayala-Orozco, PhD, the researcher who led the study, in the news release. “They’re biocompatible, stable in water, and very good at attaching themselves to the fatty outer lining of cells. But even though they were being used for imaging, people did not know how to activate these as plasmons.” 

The Rice University scientists published their findings in the journal Nature Chemistry titled, “Molecular Jackhammers Eradicate Cancer Cells by Vibronic-Driven Action.”

“The method had a 99% efficiency against lab cultures of human melanoma cells, and half of the mice with melanoma tumors became cancer-free after treatment,” according to the Rice University news release.

“I spent approximately four years working with these ideas on using molecular forces and what is called blue-light activated molecular motors,” Ciceron Ayala-Orozco, PhD (above), told Oncology Times. “At some point, I connected the dots that what I wanted to do is use a simple molecule, not necessarily a motor, that absorbs NIR light in similar ways as plasmonic nanoparticles do and go deeper into the tissue. When activated, we found that the molecules vibrate even faster than our minds can imagine and serve as a force to break the cancer cells apart.” Once approved for use treating cancer patients, clinical laboratories working with oncologists may play a key role in diagnosing candidates for the new treatment. (Photo copyright: Rice University.)

How the Technique Works

Nuclei of the aminocyanine molecules oscillate in sync when exposed to near-infrared radiation and pummel the surface of the cancer cell. These blows are so powerful they rupture the cell’s membrane sufficiently enough to destroy it. 

“The speed of this type of therapy can completely kill the cancer much faster than, say, photodynamic therapy,” Ayala-Orozco noted. “The mechanical action through the molecular jackhammer is immediate, within a few minutes.”

One advantage to near-infrared light is that it can infiltrate deeper into the body than visible light and access organs and bones without damaging tissue. 

“Near-infrared light can go as deep as 10 centimeters (four inches) into the human body as opposed to only half a centimeter (0.2 inches), the depth of penetration for visible light, which we used to activate the nanodrills,” said James Tour, PhD, T. T. and W. F. Chao Professor of Chemistry, Professor of Materials Science and NanoEngineering at Rice University, in the news release. “It is a huge advance.”

The molecular plasmons identified by the team had a near-symmetrical structure. The plasmons have an arm on one side that does not contribute to the motion, but rather anchors the molecule to the lipid bilayer of the cell membrane. The scientists had to prove that the motion could not be categorized as a form of either photodynamic or photothermal therapy

“What needs to be highlighted is that we’ve discovered another explanation for how these molecules can work,” Ayala-Orozco said in the Rice news release. “This is the first time a molecular plasmon is utilized in this way to excite the whole molecule and to actually produce mechanical action used to achieve a particular goal—in this case, tearing apart cancer cells’ membrane.

“This study is about a different way to treat cancer using mechanical forces at the molecular scale,” he added. 

New Ways to Treat Cancer

The likelihood of cancer cells developing a resistance to these molecular jackhammers is extremely low, which renders them a safer and more cost effective method for inducing cancer cell death. 

“The whole difference about this is because it’s a mechanical action, it’s not relying on some chemical effect,” Tour told KOMO News. “It’s highly unlikely that the cell will be able to battle against this. Once it’s cell-associated, the cell is toast once it gets hit by light. Only if a cell could prevent a scalpel from being able to cut it in half, could it prevent this.

“It will kill all sorts of cell types. With our other mechanical action molecules, we’ve demonstrated that they kill bacteria; we’ve demonstrated that they kill fungi. If a person has lost the ability to move a limb, if you can stimulate the muscle with light, that would be quite advantageous. Cancer is just the beginning,” he added.

“From the medical point of view, when this technique is available, it will be beneficial and less expensive than methods such as photothermal therapy, photodynamics, radio-radiation, and chemotherapy,” said Jorge Seminario, PhD, Professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University in a news release.

Researchers from Texas A&M University and the University of Texas-MD Anderson Cancer Center participated in the study. 

“This is one of the very few theoretical-experimental approaches of this nature. Usually, research in the fields related to medicine does not use first principles quantum-chemistry techniques like those used in the present work, despite the strong benefit of knowing what the electrons and nuclei of all atoms are doing in molecules or materials of interest,” Seminario noted.

“It’s really a tremendous advance. What this is going to do is open up a whole new mode of treatment for medicine,” Tour said. “It’s just like when radiation came in [and] when immunotherapy came in. This is a whole new modality. And when a new modality comes in, so much begins to open up.

“Hopefully, this is going to change medicine in a big way,” he added.

More research and clinical studies are needed before this new technology is ready for patient care. Clinical laboratories and anatomic pathology groups will likely be involved identifying patients who would be good candidates for the new treatment. These molecular jackhammers could be a useful tool in the future fight against cancer, which is ranked second (after heart disease) as the most common cause of death in the US.

—JP Schlingman

Related Information:

New Molecular Jackhammer Technique Achieves 99% Cancer Treatment Success in Labs

Scientists Destroy 99% of Cancer Cells in the Lab Using Vibrating Molecules

Molecular Jackhammers Drill Pathway to Killing Cancer Cells   

Molecular Jackhammers Eradicate Cancer Cells by Vibronic-driven Action

Molecular Jackhammers’ “Good Vibrations” Eradicate Cancer Cells

Molecular Jackhammers’ Non-Invasive Approach to Destroy Cancer Cells

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