Polymer particle shape independently influences binding and internalization by macrophages

Abstract

The interaction of macrophages with micro and nano particles (MNPs) is important because these cells clear particles from the circulation, and because they are potential therapeutic targets in inflammatory conditions, atherosclerosis and cancer. Therefore, an understanding of the features of MNPs that influence their interaction with macrophages may allow optimization of their properties for enhanced drug delivery. In this study, we show that particle shape impacts phagocytosis by macrophages, and more importantly, that particle shape and size separately impact attachment and internalization. The study provides methodology for further exploring how particle shape can be controlled to achieve desired attachment and internalization. The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages.

Design Advances in Particulate Systems for Biomedical Applications

“…Probably, the lower aspect ratio of oblate ellipsoids is related with less actin rearrangement and a faster/more effi cient internalization. [ 100 ] The effect of the shape on endocytosis by HeLa cells (from cervical cancer) was studied using cubic and cylindricalshaped PEG hydrogel particles obtained by particle replication in non-wetting templates. [ 101 ] Cubic particles with side lengths of 3 and 4 µm were not internalized whereas with 2 µm they were internalized by most cells.…”

Particle Targeting in Complex Biological Media

“…[69] Similarly, Sharma et al showed a profound impact of the particle shape on phagocytosis of PS particles by macrophages, where oblate ellipsoids were more easily internalized than prolate ellipsoids or spheres. [70] Cell attachment and internalization were influenced independently by particle shape. Prolate ellipsoids showed the highest cell attachment, but the lowest internalization rate after binding to cells, while oblate ellipsoids had the highest internalization rate after attaching but a lower overall cell attachment.…”

“…Prolate ellipsoids showed the highest cell attachment, but the lowest internalization rate after binding to cells, while oblate ellipsoids had the highest internalization rate after attaching but a lower overall cell attachment. [70] Shimoni et al reported that the human cervical cancer cell line HeLa displayed a preference for spherical polymeric capsules compared with rod-like capsules. [71] The polymeric rod-shaped capsules exhibited lower and slower cellular internalization with increasing aspect ratio (AR).…”

Controlling the morphology of copolymeric vectors for next generation nanomedicine

“…Enhanced cellular uptake has also been demonstrated as a consequence of imbuing NVs with non-spherical shapes, which needs to be investigated more extensively in order to give more extensive understanding [25]. Moreover, particle shape has been identified as a critical factor in particle uptake by phagocytes, with non-spherical morphologies giving rise to a range of behaviours [75,76]. It has also been demonstrated that the aspect ratio of rod-like NPs impacts cellular internalization, with different pathways being triggered depending upon the particle length [77].…”