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Posted: Jul 27, 2016
On-off layer-by-layer nanoassemblies for oral cancer therapy
(Nanowerk Spotlight) Oral cancer represents one of the most dreadful killer diseases globally. Researchers at Indian Institute of Technology Bombay, India have developed nano-sized layer by layer (LbL) assembled polyelectrolytes onto calcium carbonate particles to deliver small molecule tyrosine kinase inhibitors to human oral cancer cells.
Calcium carbonate (CaCO3) is a naturally occurring inorganic mineral with a porous structure generates a large surface area. It is biocompatible, biodegradable, acts as a sacrificial core template, and offers the opportunity to capture effectively a myriad molecules of interest like drugs, proteins, enzymes, etc.
The researchers encapsulated sorafenib – a tyrosine kinase inhibitor – in CaCO3 nanoparticles, which was layered alternatively with biodegradable polyelectrolytes to form a multilayer shell.
Sorafenib encapsulated on-off layer-by-layer nanoassemblies for oral cancer therapy. (Image: IIT)
The on-off sequential zeta potential cycles of polyanionic dextran sulfate and polycationic poly-L-arginine polymers ensured a compact LbL assembly on the CaCO3 nanoparticles (LbL-nanoSraf).
Physical adsorption, diffusion through pores and electrostatic interactions forms the basis for this layering assembly technique.
The researchers studied the interactions of the synthesized LbL-nanoSraf at an intracellular level.
Analysis using various biological assays revealed that this modality exhibited potent internalization of the LbL-nanoSraf in oral cancer cells resulting in strong inhibition of oral cancer cell proliferation and induced increased DNA fragmentation than free sorafenib.
Since oral carcinoma cells have high metastatic capacity, they exhibit high migratory properties. The LbL-nanoSraf potently blocked the oral cancer cell migration than sorafenib alone, thereby implicating its antimigratory potential.
"The LbL-nanoSraf displayed potent internalization of tyrosine kinase inhibitor, sorafenib leading to potent anticancer effects in oral cancer cells. Designing and promoting LbL-nanoSraf based nanomedicines is a new avenue for oral cancer therapy," concludes Dr. Radhika Poojari, the lead author of the research project.
Further exploration of this modality in in vivo studies are required, which could pave the way for many other diverse applications.