Structure-property relationship in cytotoxicity and cell uptake of poly(2-oxazoline) amphiphiles

Abstract

The family of poly(2-oxazoline)s (POx) is being increasingly investigated in the context of biomedical applications. We tested the relative cytotoxicity of POx and were able to confirm that these polymers are typically not cytotoxic even at high concentrations. Furthermore, we report structure-uptake relationships of a series of amphiphilic POx block copolymers that have different architectures, molar mass and chain termini. The rate of endocytosis can be fine-tuned over a broad range by changing the polymer structure. The cellular uptake increases with the hydrophobic character of the polymers and is observed even at nanomolar concentrations. Considering the structural versatility of this class of polymers, the relative ease of preparation and their stability underlines the potential of POx as a promising platform candidate for the preparation of next-generation polymer therapeutics.

Design Strategies for Functionalized Poly(2-oxazoline)s and Derived Materials

“…Fischer et al investigated the cytotoxicity and hemocompatibility of poly(ethylene glycol) and pEtOx under standard conditions and concluded that pEtOx presents a promising alternative for poly(ethylene glycol), since pEtOx possesses several advantages such as easier synthesis, low viscosity, and high stability [205]. The cytotoxicity of a library of poly(2-oxazoline) polymers, comprising polymers and copolymers of MeOx, EtOx, NonOx, was evaluated by Kabanov, Luxenhofer and co-workers who confirmed that this polymer class is not cytotoxic even at high concentrations [206]. The cellular uptake increased with the hydrophobic character of the polymers and was observed even at nanomolar concentrations.…”

Thermal Properties of Methyl Ester-Containing Poly(2-oxazoline)s

“…Poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx) are interesting for biomedical applications because they show stealth behaviour similar to poly(ethylene glycol) (PEG) [15,[21][22][23][24][25].…”

Biocompatibility and Immunocompatibility Assessment of Poly(2-Oxazolines)

“…It was found that cell viability was higher than 80 % for the concentration range below 1 mg/ml [61]. Structure-uptake relationships of a series of amphiphilic poly(2-oxazolines) block copolymers that have different architectures, molar mass and chain termini were reported [62]. The relative cytotoxicity of poly(2-oxazolines) was tested on MCF7-ADR cells derived from human breast carcinoma cell line, MCF7 (ATCC HT-B22).…”

“…The rate of endocytosis can be fine-tuned over a broad range by changing the polymer structure. The cellular uptake increases with the hydrophobic character of the polymers and is observed even at nanomolar concentrations [62]. Phagocytosing cells undergo a burst of oxygen consumption that is caused by an NADPH oxidase complex that assembles at the phagosomal membrane.…”