Nanoporous polymer particles (NPPs) are ideal as drug carriers because they can encapsulate large amounts of therapeutic molecules and deliver them to specific targets in the body. Understanding how these particles interact with biological cells is thus crucial for designing better drug delivery systems.

Frank Caruso and colleagues of the University of Melbourne together with co-workers from Monash University have studied how disulphide-bonded poly(methacrylic acid) (PMASH) NPPs move in HeLa cells using both flow cytometry and fluorescence microscopy. These two techniques, which basically involve looking at how fluorescently labelled particles behave in different environments, are complementary, explains team member Yan Yan of Melbourne. By combining them, we are able to obtain both quantitative and qualitative information about cell-NPP interactions, she says.

Flow cytometry, for example, allows the researchers to acquire images of thousands of cells and observe how NPPs enter these cells (and how quickly). Fluorescence microscopy, on the other hand, is used to obtain high-resolution images of single cells, and look at how NPPs interact with these cells when they undergo mitosis (or divide).

The results show that NPPs enter so-called early endosomes before passing into the cells’ lysosomes in a matter of just minutes. When the cells divide, about 80% of the NPPs enter one daughter cell and 20% the second daughter cell. “Such asymmetric partitioning is particularly important for understanding NPP–cellular dynamics and so improving particle-based drug delivery,” Yan told

This is the first study to look in detail at how NPPs segregate during mitosis and it appears that the cellular journey of particles is highly regulated by a series of intrinsic mechanisms, such as “ubiquitylation”, she added. Ubiquitylation is an enzymatic process in which ubiquitin polypeptides attach themselves to target proteins. In this particular study, the team has identified as many as 18 different proteins that may be involved.

Caruso and colleagues say they now plan to extend their investigations to other polymer particles and different types of biological cell.

The present work is reported in ACS Nano.