Polymer capsules, especially those prepared by layer-by-layer (LbL) assembly, can be used to deliver drugs inside biological cells. However, how efficient they are at this task depends on a variety of factors, such as the physical and chemical properties of the capsules, which in turn depends on their size, shape and surface chemistry. Controlling such properties is therefore an important area of research.

The aspect ratio of the capsules is an essential design parameter too, and tuning this ratio can improve how easily the particles penetrate tumour cells. Scientists have already shown that spherical gold particles (which have low aspect ratios) enter biological cells more easily than gold nanorods (which have higher aspect ratios). The same goes for spherical poly(lactide-co-glycolide) microparticles as opposed to their elliptical counterparts.

A team led by Frank Caruso has now studied how varying the aspect ratios of polymer capsules made from thiolated poly(methacrylic acid) (PMASH) and poly(N-vinyl pyrrolidone) (PVPON) affects the ability of these capsules to enter biological cells.

Making LbL polymer capsules

The researchers began by sequentially depositing multilayers of the polymers on silica templates through hydrogen bonding. Following assembly, the PMASH multilayers are stabilized by oxidation of their thiol groups to form disulphide bonds. The silica templates are then dissolved and the PVPON is released from the multilayers, resulting in the single component disulphide-bonded PMASH capsules. "Importantly, these capsules retain the original shape of the templates from which they are grown," explained team member Yan Yan. "The aspect ratios of the capsules can thus be tuned by choosing different silica templates."

Using flow cytometry and imaging flow cytometry techniques, the Melbourne team found that capsules with higher aspect ratios entered HeLa cells more slowly than those with a lower aspect ratio. Fluorescence microscopy analyses confirmed these observations.

Improving biodistribution

"Our study is just the beginning and shows how the shapes of drug-delivery capsules is important for cellular uptake," Yan told nanotechweb.org. "The fact that capsules with higher aspect ratios are internalized into cells more slowly may also help in developing techniques for improving the biodistrbution of these structures."

The researchers say that they will now be extending their experiments to other polymer systems and different biological environments. "Our future work includes developing capsules with a wider range of shapes and chemical compositions and understanding interactions not only in vitro but in vivo as well," said Yan.

The current work is detailed in ACS Nano.