Antibody-based imaging of a particularly aggressive form of breast cancer is undergoing clinical trials worldwide, but the path from trial to application is being hampered by a major obstacle: safety.
Concerns stem from inefficient tumor targeting, which can result in accumulation in the bone marrow, liver and kidneys of the radioactive material necessary for the imaging. Recent efforts have focused on nanoscale delivery vehicles with immune components, but these vehicles are often still too large (20 nanometers or larger) for renal clearance after imaging.
Researchers now have proposed a novel approach using ultrasmall silica nanoparticles - better known as "Cornell dots" (or C dots). Their team equipped the C dots with antibody fragments. Because the resulting conjugates are smaller than 8 nanometers, these C dots allow for renal clearance while achieving the specificity needed for efficient tumor targeting.They report their discovery in Nature Communications.
Cornell dots and their newer generation - termed "Cornell prime dots," or simply C' dots - have evolved since the group introduced them in 2005 and since, a first clinical trial deemed them safe for humans in 2014. Two years ago, the dots were shown to have the ability not only to detect cancer cells but to be self-therapeutic thereby actually killing them.
This latest research puts C dots back into the role of cancer-finder, but adds a "tumor finder" in the form of an antibody fragment. They used a particular fragment of the Y-shaped antibody, as opposed to the whole molecule, to keep the C' dot within the size threshold for renal clearance.
The target: HER2-positive breast cancer, more aggressive and deadly than HER2-negative cancer, making it an attractive target for new diagnostics and therapies. In the collaboration, MedImmune engineered an antibody fragment specifically to target the HER2 protein and a conjugation site not interfering with its binding activity. The dot itself was synthesized in a way that gave it five distinct functions, all within its ultrasmall size of 6 to 7 nanometers.
Both in vitro and in vivo (mouse) targeting of HER2-positive breast cancer cells were successful, with in vivo tumor uptake of the injected dots as high as 17.2 percent. "The injection circulates through the blood and has to escape the vasculature, has to diffuse through the connective tissue, has to associate with the tumor and then kind of penetrate the tumor body," the author said. "We want 100 percent - everybody wants 100 percent. But when you consider all of the other things that are competing for the vehicle elsewhere in the body, 17 percent is not that small."
http://news.cornell.edu/stories/2018/10/latest-cornell-dot-features-new-cancer-weapon-antibodies
https://www.nature.com/articles/s41467-018-06271-5
Latest News
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Mapping microbiome in metas…
By newseditor
Posted 22 Apr
Full-length mRNA packaged i…
By newseditor
Posted 22 Apr
Glucose-sensing mechanism t…
By newseditor
Posted 21 Apr
Other Top Stories
Unknown way cells protect their genomes during replication
Read more
Modeling TGF-β signaling in human skin
Read more
Afternoon chemotherapy improves treatment outcomes in female lympho…
Read more
A new DNA repair mechanism that hinders cancer treatment
Read more
How tumor suppressor loss enhances breast cancer
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Neuronal activity rapidly r…
By newseditor
Posted 22 Apr
A perspective on muscle phe…
By newseditor
Posted 22 Apr
Foxp1 suppresses cortical a…
By newseditor
Posted 22 Apr
Single-cell long-read seque…
By newseditor
Posted 22 Apr
Unlocking potential: the ro…
By newseditor
Posted 22 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar