The in vitro and in vivo properties of ringlike polymer brushes

Cyclic polymers have an intriguing endless architecture and exhibit unique biological properties. However, the reported cyclic polymers either adopt loosely curled conformations or exist in closely packed states, and thus their distinct biological properties are mostly attributed to their endless feature or different packing behaviors and not directly related to the ringlike morphology. Up to now, the biological properties of the polymers with a ringlike morphology still remain unknown. Herein, for the first time, we investigate the in vitro and in vivo properties of the cyclic cylindrical polymer brushes (CPBs) with a ringlike morphology and present an important finding that cyclic CPBs are more prone to non-specific protein adsorption than their linear counterparts with the same chemical composition and contour length due to their lower flexibility. This finding can explain the fact that although cyclic CPBs have lower cellular uptake in different cell lines and lower phagocytosis in macrophage cells than linear CPBs, they exhibit relatively shorter blood circu-lation and higher liver and spleen uptake, which further leads to lower tumor accumulation. Additionally, we also found that the endless character of cyclic CPBs imparted to them lower tumor permeability. Even so, the cyclic CPBs still exhibited excellent passive tumor targeting ability and their tumor uptake reached about 8.2% of the injected dose per gram of tissue (ID/g) after a single intravenous administration. These fundamental findings have important implications not only for a deeper understanding of cyclic polymers but also for guiding the design of biomaterials. (c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

This study investigated the properties of cyclic cylindrical polymer brushes (CPBs) with a ringlike morphology for the first time and found that they are more prone to non-specific protein adsorption compared to their linear counterparts. Despite lower cellular uptake and tumor permeability, cyclic CPBs exhibited excellent passive tumor targeting ability and achieved a tumor uptake of about 8.2% of the injected dose per gram of tissue after a single intravenous administration.