Chitosan-Coated, Chemotherapy-Packed Nanoparticles May Target Cancer Stem-Like Cells
Nanoparticles packed with a clinically used chemotherapy drug and coated with an oligosaccharide derived from the carapace of crustaceans might target and kill cancer stem-like cells, according to a study led by researchers at the OSUCCC – James.
Cancer stem-like cells have characteristics of stem cells and are present in very low numbers in tumors. They are highly resistant to chemotherapy and radiation, and they are believed to play an important role in tumor recurrence. This laboratory and animal study showed that nanoparticles coated with an oligosaccharide called chitosan and encapsulating the chemotherapy drug doxorubicin can target and kill cancer stem-like cells six times more effectively than free doxorubicin.
“This nanoparticle delivery system increased the cytotoxicity of doxorubicin with no evidence of systemic toxic side effects in our animal model,” says principal investigator Xiaoming (Shawn) He, PhD, associate professor of Biomedical Engineering at Ohio State and a member of the Translational Therapeutics Program at the OSUCCC – James. “We believe that chitosan-decorated nanoparticles could also encapsulate other types of chemotherapy and be used to treat many types of cancer.”
The study showed that chitosan binds with the CD44 receptor on cancer stem-like cells, enabling the nanoparticles to target the malignant stem-like cells in a tumor.
The nanoparticles were engineered to shrink, break open and release the anticancer drug under the acidic conditions of the tumor microenvironment and in tumor-cell endosomes and lysosomes, which cells use to digest nutrients.
He and his colleagues conducted the study using models called 3D mammary tumor spheroids (i.e., mammospheres) and an animal model of human breast cancer.
The study also found that, although the drug-carrying nanoparticles could bind to the variant CD44 receptors on cancerous mammosphere cells, they did not bind well to the CD44 receptors that were overexpressed on noncancerous stem cells.
Reported in the journal ACS Nano.
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