Squaric Ester‐Based Nanogels Induce No Distinct Protein Corona but Entrap Plasma Proteins into their Porous Hydrogel Network

Abstract

Front Cover: In article number 2200318, Lutz Nuhn and co‐workers incubate squaric ester‐based nanogels with blood plasma for characterizing the particles' protein corona. However, no increase in size nor aggregation is found, and only few proteins (3 wt%) can be identified of similar composition to their proportion in native plasma. Due to the nanogels' hydrated and porous network morphology, it is concluded that the detected proteins result from passive diffusion into the nanogel. The cover image was designed by Katharina Maisenbacher.

Post‐Polymerization Modifications to Prepare Biomedical Nanocarriers with Varying Internal Structures, their Properties and Impact on Protein Corona Formation

“…Recent experiments demonstrated, however, that such nano(hydro)gels absorb only very little plasma proteins when they are made from highly polar and stealth polymers. [87] For the squarogel system with short PEG chains inside the core, their tendency to adsorb plasma proteins is comparably as low as what we observed also for block copolymer micelles (Figure 5 and Figure 6). [56] However, there was a significant difference in the class of the plasma proteins that were found after separation by AF4 and subsequent proteomic analysis by mass spectrometry.…”

“…For that purpose, we more recently introduced the squaric ester amide technology as an attractive alternative to performing a nano(hydro)gels synthesis in water affording so-called squarogels. [73,85,87,88] Due to the high sensitivity to amines but hydrolytic resistance of the squaric ester amides in water, respec-Scheme 1. Reaction scheme for the preparation of poly(norbornene)-nano(hydro)gels.…”

“…The alendronate-loaded squarogels promoted an improved delivery of the bisphosphonate to immunosuppressive macrophages in fibrotic livers and thereby repolarized their phenotype in order to prevent liver fibrosis disease progression. [73,85,87,88] As a result of all these different studies, one should take into account that a large variety of nanoparticles with different structures can be prepared from block copolymers bearing amine reactive blocks: Beyond polymeric micelles with a hydrophobic core (Figure 1), polymeric nano(hydro)gels seem to be very robustly reproduced by this strategy (Figure 2). Although the inner part can chemically differ from each other, upon core-crosslinking and hydrophilization it can provide nano(hydro)gels of comparable inner and outer hydrophilicity as well as inner mechanical property.…”

“…For that purpose, we more recently introduced the squaric ester amide technology as an attractive alternative to performing a nano(hydro)gels synthesis in water affording so‐called squarogels. [ 73,85,87,88 ] Due to the high sensitivity to amines but hydrolytic resistance of the squaric ester amides in water, respective methacrylamide monomers could be generated and RAFT‐polymerized onto poly(ethylene glycol) macro‐chain transfer agents. Upon micellar self‐assembly in water, the resulting precursor micelles were subsequently converted via treatment with bis(2‐aminoethyl) ketals into acid‐degradable nano(hydro)gels ( Scheme ).…”

“…The alendronate‐loaded squarogels promoted an improved delivery of the bisphosphonate to immunosuppressive macrophages in fibrotic livers and thereby repolarized their phenotype in order to prevent liver fibrosis disease progression. [ 73,85,87,88 ]…”