Disguising Nanoparticles May Improve Chemotherapy Delivery

Targeted cancer treatment has proven difficult due to the fact that the molecule needs to be sturdy enough to get through the bloodstream and flexible enough to enter the tumor’s extra cellular space.

Researchers believe that disguising nanoparticles may trick a cancerous tumor in order to gain entry, according to a study published by Nano Letters.

"What we've reported here is a strategy to overcome biological barriers that plague delivery of medication, such as nonvehicle clearance in the bloodstream by the host immune system, and ineffective diffusion in the extracellular matrix of tumor cells," said researcher Hao Cheng, PhD said in a press release. "It's a unique strategy that involves the decoration of nanovehicles with enzymes known to break down hyaluronic acid, which is a main barrier in the extracellular space, and the addition of an extra layer of polyethylene glycol to partially cover the enzymes."

Investigators found this method is 4 times more successful at sending nanoparticles into a solid tumor than the best current strategy.

Also, research has shown that when the nanoparticle contains cancer medication, it can inhibit the growth of an aggressive form of breast cancer.

"In the general design of nanoparticles, bioactive molecules -- not limited to enzymes -- were attached on the outermost layer of particles," Cheng said. "These enzymes can degrade the extra cellular matrix and enhance the nanoparticle's ability to penetrate solid tumors."

One potential issue is that attaching enzymes to nanoparticles can cause them to not reach the tumor and be cleared by the bloodstream.

Researchers also note that the bloodstream could also immobilize the enzymes.

In order to combat these potential issues, researchers added an extra layer to protect the cancer medication inside and position the enzymes in a way that provides maximum impact.

Researchers embedded hyaluronidase enzymes in layers of poluethylene glycol to make sure that the nanoparticle can be bypassed by the immune system. This also allows the particle to deal with hyaluronic acid when it enters the tumor.

This method is more effective because of the retention of enzymes throughout the duration of their diffusion into the tumor. This eliminates any unnecessary hyaluronic acid degradation.

"The degradation of hyaluronic acid removes the barrier for nanoparticles to diffuse and allows them to access more cancer cells," Cheng said. "The enhanced diffusion also increases the accumulation of nanoparticles in tumors, and the more nanoparticles that get into tumors the more effective they are at reducing its size."

The researchers tested their nanoparticles against other ones which did not have an additional layer of polyethylene glycol and ones which did not have ECM-degrading enzymes.

Their molecule outperformed the others in regards to penetrating the tumors and accumulating in the cancer cells.

In the future, researchers see immense potential for their method to treat difficult cancers.