Research led by the University of Pennsylvania, Philadelphia, has used siRNA-based silencing of protein cyclophilin A (CyPA) to reduce tumor burden and extend the lives of patients with multiple myeloma.
Multiple myeloma (MM) is a blood cancer that occurs in the bone marrow and can form tumors outside bone marrow in the body’s organs (extramedullary disease). MM is currently treatable but incurable, with inevitable relapse after treatment and typically short survival rates of 3 to 6 months for those with relapse as they build resistance to the treatments.
Endothelial cells within the bone marrow microenvironment are thought to play a critical role. Specifically, cyclophilin A (CyPA), a protein secreted by bone marrow endothelial cells, is involved in progression, survival, and chemotherapeutic resistance.
Inhibiting CyPA could simultaneously inhibit MM progression and make MM more vulnerable to chemotherapeutics, but getting inhibiting molecules into the bone marrow endothelium is challenging.
Small interfering RNA (siRNA) therapeutics have broad potential to silence any targeted gene and are a great candidate for CyPA silencing but are limited by instability in the bloodstream and an inability to traverse cell membranes easily.
The researchers needed a way to get the potential therapy to the correct location and turned to a nanoparticle delivery system. The team developed nanoparticles comprised of a polymer-lipid hybrid material and a lipid-polyethylene glycol (PEG) to enable nucleic acid encapsulation.
The nanoparticles reduced the degradation of the RNA by enzymes in the blood and were able to deliver the payload siRNA to specific tissues via functionalization of the nanoparticle surface chemistry,
The nanoparticle delivery platform and a CyPA silencing siRNA payload were deployed in a living mouse model, and it worked. The silencing of CyPA decreased multiple myeloma invasion across bone marrow endothelial cells and disrupted interactions. When combined with a therapeutic, bortezomib, CyPA silencing sensitized cancer cells to therapy, which reduced proliferation and angiogenesis, and ultimately extended mouse survival.
The authors suggest that this nanoparticle platform may provide a broadly enabling technology to deliver nucleic acid therapeutics to other malignancies.
News
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
Chernobyl scientists discover black fungus feeding on deadly radiation
It looks pretty sinister, but it might actually be incredibly helpful When reactor number four in Chernobyl exploded, it triggered the worst nuclear disaster in history, one which the surrounding area still has not [...]
Long COVID Is Taking A Silent Toll On Mental Health, Here’s What Experts Say
Months after recovering from COVID-19, many people continue to feel unwell. They speak of exhaustion that doesn’t fade, difficulty breathing, or an unsettling mental haze. What’s becoming increasingly clear is that recovery from the [...]
Study Delivers Cancer Drugs Directly to the Tumor Nucleus
A new peptide-based nanotube treatment sneaks chemo into drug-resistant cancer cells, providing a unique workaround to one of oncology’s toughest hurdles. CiQUS researchers have developed a novel molecular strategy that allows a chemotherapy drug to [...]
Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”
An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs. How does your brain recognize when it’s time to take a breath, when your blood pressure has [...]
Scientists Discover a New Form of Ice That Shouldn’t Exist
Researchers at the European XFEL and DESY are investigating unusual forms of ice that can exist at room temperature when subjected to extreme pressure. Ice comes in many forms, even when made of nothing but water [...]
Nobel-winning, tiny ‘sponge crystals’ with an astonishing amount of inner space
The 2025 Nobel Prize in chemistry was awarded to Richard Robson, Susumu Kitagawa and Omar Yaghi on Oct. 8, 2025, for the development of metal-organic frameworks, or MOFs, which are tunable crystal structures with extremely [...]
Harnessing Green-Synthesized Nanoparticles for Water Purification
A new review reveals how plant- and microbe-derived nanoparticles can power next-gen water disinfection, delivering cleaner, safer water without the environmental cost of traditional treatments. A recent review published in Nanomaterials highlights the potential of green-synthesized nanomaterials (GSNMs) in [...]
Brainstem damage found to be behind long-lasting effects of severe Covid-19
Damage to the brainstem - the brain's 'control center' - is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests. Using ultra-high-resolution scanners that can see the living brain in [...]
CT scan changes over one year predict outcomes in fibrotic lung disease
Researchers at National Jewish Health have shown that subtle increases in lung scarring, detected by an artificial intelligence-based tool on CT scans taken one year apart, are associated with disease progression and survival in [...]
AI Spots Hidden Signs of Disease Before Symptoms Appear
Researchers suggest that examining the inner workings of cells more closely could help physicians detect diseases earlier and more accurately match patients with effective therapies. Researchers at McGill University have created an artificial intelligence tool capable of uncovering [...]
Breakthrough Blood Test Detects Head and Neck Cancer up to 10 Years Before Symptoms
Mass General Brigham’s HPV-DeepSeek test enables much earlier cancer detection through a blood sample, creating a new opportunity for screening HPV-related head and neck cancers. Human papillomavirus (HPV) is responsible for about 70% of [...]
Study of 86 chikungunya outbreaks reveals unpredictability in size and severity
The symptoms come on quickly—acute fever, followed by debilitating joint pain that can last for months. Though rarely fatal, the chikungunya virus, a mosquito-borne illness, can be particularly severe for high-risk individuals, including newborns and older [...]
Tiny Fat Messengers May Link Obesity to Alzheimer’s Plaque Buildup
Summary: A groundbreaking study reveals how obesity may drive Alzheimer’s disease through tiny messengers called extracellular vesicles released from fat tissue. These vesicles carry lipids that alter how quickly amyloid-β plaques form, a hallmark of [...]
Ozone exposure weakens lung function and reshapes the oral microbiome
Scientists reveal that short-term ozone inhalation doesn’t just harm the lungs; it reshapes the microbes in your mouth, with men facing the greatest risks. Ozone is a toxic environmental pollutant with wide-ranging effects on [...]
New study reveals molecular basis of Long COVID brain fog
Even though many years have passed since the start of the COVID-19 pandemic, the effects of infection with SARS-CoV-2 are not completely understood. This is especially true for Long COVID, a chronic condition that [...]
