Researchers at Penn State working with collaborators have developed a nanomaterial that can ‘mop up’ chemotherapeutics in the bloodstream, helping to reduce off-target effects. The technology is intended for use in situations where a chemotherapeutic can be delivered precisely to the site of a tumor, and not in situations where it is delivered systemically. The cellulose particles have a large number of polymer chain “hairs” that protrude from each end, that increase their ability to bind drug molecules in the blood. Chemotherapy can be incredibly difficult for patients who undergo treatment, with an extensive list of serious side-effects caused by off-target toxicity in the body. Researchers are in the process of refining chemotherapy delivery by developing an array of nanoparticles and biomaterial carriers that are intended to reduce the amount of free drug that reaches systemic circulation and to maximize efficacy at a tumor site. One such advanced approach involves delivering chemotherapy directly to the site of a tumor using a catheter. So far, this is most suited for tumors in certain organs, such as the liver, where the drug can be released into a blood vessel that carries blood directly to the organ. However, while the drug is released near the target site, much of it still ends up escaping into the systemic circulation and causes side-effects. This is where “clean-up” technology could play a role. This approach aims to bind the free drug in the circulation, rendering it largely harmless. However, current methods to achieve this are suboptimal. “To reduce the off-target effects of cancer drugs during and after localized chemotherapy, eliminating their systemic circulation is necessary,” said Amir Sheikhi, a researcher involved in the latest study. “Available and proposed platforms to remove unwanted drugs – primarily the chemotherapy drug doxorubicin (DOX) – from blood are exceedingly ineffective, failing to remove enough of the drug to prevent damage. We have developed a highly efficient approach that captures DOX at a capacity more than 3,200% higher than other platforms, such as DNA-based materials.” This new technology consists of cellulose, a key constituent of plant cell walls. To create the hairy crystals, the researchers chemically treated cellulose derived from softwood pulp, and gave it a negative charge, meaning that it is more stable when present in the blood and also allows it to bind positively charged drug molecules, such as doxorubicin. So far, the researchers have shown that 1 gram of the particles can bind approximately 6 grams of doxorubicin in serum. “We found that the hairy cellulose nanocrystals bind to positively charged drugs in human serum and capture DOX immediately, and they do so without imposing any cytotoxicity or hemolytic effects,” said Sheikhi. “We envision that this effective, non-toxic nanoparticle could be a building block for the next generation of devices to capture excess drugs and remove unwanted molecules from the body, such as psychedelics and toxins.” Source
