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
Fever-Proof Bird Flu Variant Could Fuel the Next Pandemic
Bird flu viruses present a significant risk to humans because they can continue replicating at temperatures higher than a typical fever. Fever is one of the body’s main tools for slowing or stopping viral [...]
What could the future of nanoscience look like?
Society has a lot to thank for nanoscience. From improved health monitoring to reducing the size of electronics, scientists’ ability to delve deeper and better understand chemistry at the nanoscale has opened up numerous [...]
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
