Stealth Effect of Short Polyoxazolines in Graft Copolymers: Minor Changes of Backbone End Group Determine Liver Cell-Type Specificity

Abstract

Dye-loaded micelles of 10 nm diameter formed from amphiphilic graft copolymers composed of a hydrophobic poly­(methyl methacrylate) backbone and hydrophilic poly­(2-ethyl-2-oxazoline) side chains with a degree of polymerization of 15 were investigated concerning their cellular interaction and uptake in vitro as well as their interaction with local and circulating cells of the reticuloendothelial system in the liver by intravital microscopy. Despite the high molar mass of the individual macromolecules (M n ≈ 20 kg mol–1), backbone end group modification by attachment of a hydrophilic anionic fluorescent probe strongly affected the in vivo performance. To understand these effects, the end group was additionally modified by the attachment of four methacrylic acid repeating units. Although various micelles appeared similar in dynamic light scattering and cryo-transmission electron microscopy, changes in the micelles were evident from principal component analysis of the Raman spectra. Whereas an efficient stealth effect was found for micelles formed from polymers with anionically charged or thiol end groups, a hydrophobic end group altered the micelles’ structure sufficiently to adapt cell-type specificity and stealth properties in the liver.

Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence‐Defined Components

“…Literature could show that different polymer end groups can have a decent impact on cellular uptake [82,83] and in vivo performance. [84] Jordan Green and co-workers could show that small molecule end group modifications of linear polymers can influence cellular uptake behavior largely independent of polymer/DNA binding, particle size, and particle surface charge. [82,83] Bekale et al investigated PEG end group effects on the interaction with model proteins (human and bovine serum albumin) in order to comprehend the relationship between structural properties of PEG and polymer affinity toward proteins.…”

Reincarnation of the Analytical Ultracentrifuge: Emerging Opportunities for Nanomedicine

“…Existence of micelles containing cargo was found down to concentrations as expected by the dilution in the blood volume of mice. This was indicated by hydrodynamic diameter (eq ) and molar mass (right-hand side of eq S5) estimations from AUC data …”

“…In a follow-up study, focusing on related materials, the polymer backbone end-group chemistry was also shown to impact the stealth and cell-type specific behavior of micelles in mice. 58 Existence of micelles containing cargo was found down to concentrations as expected by the dilution in the blood volume of mice. This was indicated by hydrodynamic diameter (eq 6) and molar mass (right-hand side of eq S5) estimations from AUC data.…”

“…The authors studied the molar mass of unimeric species, i.e., the polymers in a good solvent for the polymer, and that of micelle structures in water including determination of the partial specific volume, υ. Conclusively, and by making use of intrinsic estimates of s , i.e., [ s ] (eq ) and the modified Svedberg equation (right-hand side of eq S5), they found that, depending on the initial polymer composition, the degree of aggregation of polymers could be designed to result in numbers of aggregation up to roughly ten in an aqueous solution. In a follow-up study, focusing on related materials, the polymer backbone end-group chemistry was also shown to impact the stealth and cell-type specific behavior of micelles in mice . Existence of micelles containing cargo was found down to concentrations as expected by the dilution in the blood volume of mice.…”

“…This was indicated by hydrodynamic diameter (eq 6) and molar mass (right-hand side of eq S5) estimations from AUC data. 58 While PEGs have been intensively investigated with the AUC and related techniques, 51 fundamental studies can be considered essential for the creation of advanced polymer systems. For instance, Klein et al synthesized four benzene-1,3,5-tricarboxamides (BTA)-PEGs (Figure 3, top).…”