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Journey to the Centre of the Cell

When it comes to delivering drugs, nanoparticles shaped like rods and worms are the best bet for making the daunting journey to the centre of a cell, according to research published in Nature Nanotechnology.

“We were able to show for the first time that nanoparticles shaped like rods and worms were more effective than spherical nanoparticles at traversing intracellular barriers, and this enabled them to get all the way into the nucleus of the cell,” says lead author Dr Elizabeth Hinde of UNSW Australia.

The research team applied a new microscopy method that allowed them to track the movement of differently shaped nanoparticles through a single cultured cancer cell. They were able to pinpoint where drugs were being released and how they spread throughout the cell.

They found that the cancer drug doxorubicin was most effective when it could breach the strong yet porous cellular barrier protecting the nucleus. Importantly, they discovered that the nanoparticle’s shape – a rod, worm or sphere – influenced how well the drug breached the barrier.

Hinde explains that researchers could previously see the overall distribution of their nanoparticles throughout a cell, but didn’t have the microscopy tools to understand how this localisation was set up – a key limitation in drug delivery research. “You need to know how things arrive at their final destination in order to target them there. Now we have a tool to track this incredible journey to the centre of the cell.

“It means other research groups can use this to assess their nanoparticles and drug delivery systems. They’ll be able to work out how to tailor their particles to reach the nucleus or other structures in the cell, and gauge where the cargo is being dropped off. This wasn’t possible before.”

UNSW engineers fabricated four types of nanoparticles: one shaped like a rod, one like a worm, and two that were spherical in shape. These were labelled with fluorescent tags, and incubated in cancer cells.

While the spherical particles were blocked by the nuclear envelope, the rod and worm-shaped particles were able to pass through. This provides a pathway for the development of particles that can selectively target and kill cancer cells without hurting healthy ones.

“Cancer cells have different internal architecture than healthy cells,” Hinde explains. “If we can fine-tune the dimensions of these rod-shaped nanoparticles, so they only pass through the cellular barriers in cancer cells and not healthy ones, we can reduce some of the side-effects of chemotherapies.”