Researchers have identified a vitamin B12–based compound that appears capable of crossing the blood–brain barrier and selectively accumulating in glioblastoma tissue.
For decades, one of the biggest problems in brain cancer treatment has had little to do with killing cancer cells and everything to do with reaching them. The brain’s protective blood-brain barrier (BBB) blocks toxins and pathogens from entering the brain, but it also prevents many cancer drugs from getting through.
That challenge has helped make glioblastoma one of the deadliest forms of cancer, with most patients surviving little more than a year after diagnosis despite aggressive treatment.
Now, researchers report early evidence that a modified form of vitamin B12 may be able to slip through that barrier and deliver a cancer-fighting molecule directly into brain tumors.
The findings, published in Oncoscience, focus on nitrosylcobalamin (NO-Cbl), a nitric oxide-releasing vitamin B12 analog. The study was led by Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center.
Evaluating NO-Cbl Across Multiple Models
Researchers tested NO-Cbl using several experimental methods, including the NCI-60 human tumor cell line panel, pharmacokinetic studies in rats with glioblastoma tumors, and combination therapy studies in human glioblastoma cell lines.
The results showed that NO-Cbl produced antitumor effects across multiple cancer types. Central nervous system tumor cell lines showed moderate sensitivity to the treatment.
Animal studies revealed that NO-Cbl successfully crossed the BBB after systemic administration and accumulated preferentially in glioblastoma tissue. Tumor nitrate levels stayed elevated for at least 24 hours after treatment, while nitrate levels in normal tissues declined more quickly. These findings suggest that the compound may provide targeted nitric oxide delivery within the tumor microenvironment.
They also showed sustained accumulation of nitrate and cobalamin-related metabolites in brain tumor tissue compared with other organs.
Enhanced Effects With Existing Therapies
The researchers also investigated whether NO-Cbl could improve the effectiveness of current glioblastoma treatments. In cultured U87 and D54 glioblastoma cells, combining NO-Cbl with TRAIL or temozolomide produced significantly greater suppression of tumor cell proliferation than either treatment alone.
Combination index analysis confirmed synergistic interactions across multiple dose ranges.
“This pilot study demonstrates that NO-Cbl crosses the BBB, accumulates selectively in brain tumor tissue, and synergizes with established and experimental glioblastoma therapies,” the authors say.
Possible Role in Overcoming Drug Resistance
The study also examined how NO-Cbl may help counter treatment resistance in glioblastoma. Previous research cited by the authors showed that the compound can trigger apoptosis through caspase-8 activation, suppress NF-κB survival signaling, and enhance TRAIL receptor signaling through S-nitrosylation.
Together, these mechanisms may improve treatment sensitivity, including in temozolomide-resistant glioblastoma models.
The authors emphasized that the work is an early translational pilot study and that more research will be needed before the approach can move toward clinical use. Future studies will focus on orthotopic validation, dose optimization, long-term nitric oxide tracking, and additional mechanistic studies in central nervous system tumor models.
Overall, the findings provide early evidence that a cobalamin-based nitric oxide donor could represent a new therapeutic strategy for glioblastoma. By combining BBB penetration, tumor-targeted nitric oxide delivery, and synergy with existing therapies, NO-Cbl may help improve drug delivery and reduce treatment resistance in one of the most difficult cancers in neuro-oncology.
Reference: “Selective blood-brain barrier penetration and tumor targeting of nitrosylcobalamin in glioblastoma: Pharmacokinetics, tissue distribution, and synergistic activity with trail and temozolomide” by Joseph A Bauer, Annette M Sysel and Michael J Dunphy, 2 April 2026, Oncoscience.
DOI: 10.18632/oncoscience.654
News – Curated by Amanda Scott, Alias Group Creative
Follow her on Bluesky
Optogenetics Pioneers Win 2026 Nobel Prize in Physiology or Medicine
The 2026 Nobel Prize in Physiology or Medicine has been awarded to Peter Hegemann, Georg Nagel, and Karl Deisseroth for the development of optogenetics, a revolutionary technology that uses light to control individual neurons [...]
Molecular Manufacturing: The Future of Nanomedicine – From NanoappsMedical Inc.
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
What is ‘American Covid’ and how bad is it?
Cases of so-called ‘American Covid’ are on the rise in the UK. The strain is officially called XFG, or ‘Stratus’, and is the most common variant in North America, hence the name. It might soon [...]
Researcher at Russian plague laboratory dies of ‘unknown’ infection
Russian authorities have imposed "anti-epidemic measures" after a laboratory worker at an institute in Siberia dedicated to studying the plague and other infectious diseases died of a mysterious illness. The researcher, a 28-year-old female [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
A Surprising Brain Signal Could Explain Why Eating Less Protein Extends Lifespan
A new paper suggests that limiting protein intake triggers a coordinated response throughout the body that may help explain how protein restriction affects healthy aging. Animals respond to protein restriction, or reduced protein in [...]
Back and shoulder surgery is often worse than useless
Millions of operations should be scrapped SIX IN TEN Britons have surgery at some point. So do lots of Americans, at a cost of perhaps $500bn a year, a third of all spending on [...]
Cocaine plays with mind, hijacks brain circuit, drives increasingly rigid and repetitive behavior
Researchers have found that cocaine hijacks brain circuit, which to drive increasingly rigid and repetitive behavior. The brain circuit that normally participates in selecting natural mouth and face movements, but which becomes disproportionately engaged [...]
Injectable nanodevices could provide effective treatment for drug-resistant glioblastoma
The brain cancer glioblastoma is one of the most aggressive and treatment-resistant cancers known to medicine, carrying a median survival of just 12-15 months, even with the best available care. Now, researchers at the [...]
New Treatment Cuts “Bad” Cholesterol in Half for a Full Year
A single infusion of an experimental CRISPR-Cas9 therapy was reported to safely lower LDL cholesterol by 52.5% and triglycerides by 47.8%, as measured 12 months after treatment. What if one infusion could keep cholesterol [...]
Too Much RNA Can Drain a Cell’s Energy, Scientists Discover
A virus may cripple a cell’s power supply simply by producing too much of a molecule the cell needs to survive. New research from the Texas A&M College of Veterinary Medicine and Biomedical Sciences [...]
West African scientists warn of weakening health systems and urge stronger outbreak detection
LOME, Togo (AP) — West African laboratory scientists called on governments Friday to strengthen capacity to detect disease outbreaks to avoid another major outbreak, saying health systems across the region are becoming weaker. Participants [...]
A Little-Known Protein Could Point to a New Way To Treat Alzheimer’s
A study suggests that increasing SORLA protein levels could help treat Alzheimer’s disease and other disorders involving tau protein. Increasing SORLA, a protein with a protective role in the brain, helped mice withstand damage [...]
Cancer’s Hidden Antioxidant Shield Helps It Escape the Immune System
Blocking an antioxidant protein that tumors use to suppress immune attacks improved cancer immunotherapy responses in mice. Cancer cells can release antioxidants that interfere with the immune cells trying to kill them. Researchers have [...]
Scientists Find a Berry Compound That Helps Muscle Cells Burn Fat
Pterostilbene, a compound found naturally in some foods, affects how skeletal muscles process fats by stabilizing a protein called PPARδ and increasing its signaling activity. Pterostilbene, a natural compound found in blueberries, grapes, and [...]
Two Hidden Forces Help Build the Human Brain Before Birth
Scientists have uncovered two surprising forces that help guide how the human brain forms before birth. Before birth, the human brain is shaped in large part by an unusual class of stem cells known [...]
