DREXEL UNIVERSITY, PHILADELPHIA, USA AND SACRAMENTO, CALIFORNIA, USA. Drexel University researchers’ new method of accessing the cellular masses of a tumor by giving nanoparticles a new look has been found to be four times more effective at delivering nanoparticles into a solid tumor than one of the current best strategies being used.

Various biomedical researchers have been searching for better ways to deliver effective medication to tumors in the human body. This challenge has been an ongoing battle for years already. The group of researchers, headed by Hao Cheng, is continuously figuring out the best way for particles to get past the tumor’s biological bouncers and to come up with a sturdy vehicle that will deliver the medication safely through the bloodstream to tumors. However, this sturdy vehicle must also be supple enough to squeeze through the tumor’s dense extracellular space – a matrix abundant in sugars called hyaluronic acid.

Through extensive research, the group determined that the way to enter a tumor depends on how tiny the particle is suited up for the delivery. They needed a strategy to overcome biological barriers that hinder the delivery of medication such as non-vehicle clearance in the bloodstream by the host immune system, and ineffective diffusion in the extracellular matrix of tumor cells. Researchers from various colleges in Drexel University created their nanoparticle by starting with one that is common in the area of cancer research and making some key changes to it.

The group strategized decorating nanovehicles with enzymes known to break down hyaluronic acid which is a main barrier in the extracellular space, and adding an extra layer of polyethylene glycol (PEG) to partially cover the enzymes. Aside from enzymes, they also attached bioactive molecules on the outermost layer of particles to enhance the penetration to solid tumors. However, attaching these enzymes to nanoparticles could prevent them from having successful delivery to the tumor.

To solve this issue, the team added an extra layer to protect the precious payload and, more importantly, position the enzymes for maximum impact and result. In detail, the group has embedded the hyaluronidase enzymes in a second PEG layer to form the outer shell of the nanoparticle. This process decreases the enzymes’ effect on slowing the particle’s circulation and allows enzymes to retain their purpose after the particle diffuses inside the tumor. Having the enzymes with the layers of PEG ensures that the nanoparticle tricks the immune system into leaving it alone during its way to the tumor but it should still allow the particle to deal with any hyaluronic acid it will encounter upon its penetration of the tumor.

Other studies have tested a theory that exposes tumors to the enzymes first and then to nanoparticles. However, this is not nearly as effective as Drexel University’s method because the nanoparticles they developed retain the enzymes through the duration of their diffusion into tumors, minimizing unnecessary hyaluronic acid degradation, thus preventing failure in the penetration to the tumor.

As for the benefits of this research, the group’s invention removes the barrier for nanoparticles to diffuse and positively allows them to access more cancer cells in the human body, unlike previous methods. This diffusion allows the increase in accumulation of nanoparticles in tumors. The more nanoparticles that get into tumors, the more effective they are at reducing its size. The nanoparticle developed by the Drexel group performed better in both penetrating tumors and accumulating in cancerous cells.

Prospectively, an enormous potential for this strategy is being foreseen in the medicinal setting for a number of difficult-to-treat cancers in the world such as locally advanced breast, pancreatic and mucin-inducing gastrointestinal cancers.

Image courtesy of pixabay.com

Learn more about PreScouter at www.prescouter.com.