Analysing intracellular deformation of polymer capsules using structured illumination microscopy

Abstract

Understanding the behaviour of therapeutic carriers is important in elucidating their mechanism of action and how they are processed inside cells. Herein we examine the intracellular deformation of layer-by-layer assembled polymer capsules using super-resolution structured illumination microscopy (SIM). Spherical- and cylindrical-shaped capsules were studied in three different cell lines, namely HeLa (human epithelial cell line), RAW264.7 (mouse macrophage cell line) and differentiated THP-1 (human monocyte-derived macrophage cell line). We observed that the deformation of capsules was dependent on cell line, but independent of capsule shape. This suggests that the mechanical forces, which induce capsule deformation during cell uptake, vary between cell lines, indicating that the capsules are exposed to higher mechanical forces in HeLa cells, followed by RAW264.7 and then differentiated THP-1 cells. Our study demonstrates the use of super-resolution SIM in analysing intracellular capsule deformation, offering important insights into the cellular processing of drug carriers in cells and providing fundamental knowledge of intracellular mechanobiology. Furthermore, this study may aid in the design of novel drug carriers that are sensitive to deformation for enhanced drug release properties.

Template‐Mediated Assembly of DNA into Microcapsules for Immunological Modulation

“…Previous studies have shown that soft polymeric capsules inside cells are deformed upon ingestion because of the mechanical stress exerted by the cell membrane. [ 42,43 ] The acquired images suggest that RAW264.7 cells can exert high shear forces on CpG cap during their internalization. As CpG cap are highly hydrated, hollow, and flexible, they are prone to deformation upon internalization.…”

Super-resolution microscopy as a powerful tool to study complex synthetic materials

“…A relevant example is the particle deformation following internalization due to mechanical stress. Caruso and coworkers reported on the use of SIM to image the deformation of polymer capsules occurring inside cells 135 . Hollow spheres are more susceptible to mechanical stress and a high degree of compression was observed in different cell lines irrespective of the capsule shape, suggesting that the forces are cell-dependent.…”

Super-resolution Microscopy for Nanomedicine Research

“…As an example, structure illumination microscopy (SIM) has been used to monitor particle deformation during internalization. 40 Interestingly, different cell lines exert different mechanical forces, inducing a proportional polymer capsule’s shrinkage. Moreover, the stability of supramolecular aggregates in serum and in cells can be followed by STORM, revealing in what state (assembled or disassembled) the carriers reach different locations.…”