Next‐Generation Polymer Shells for Inorganic Nanoparticles are Highly Compact, Ultra‐Dense, and Long‐Lasting Cyclic Brushes

Abstract

Cyclic poly-2-ethyl-2-oxazoline (PEOXA) ligands for superparamagnetic Fe 3 O 4 nanoparticles (NPs) generate ultra-dense and highly compact shells,p roviding enhanced colloidal stability and bio-inertness in physiological media. When linear brush shells fail in providing colloidal stabilization to NPs,t he cyclic ones assure long lasting dispersions. While the thermally induced dehydration of linear PEOXA shells cause irreversible aggregation of the NPs,t he collapse and subsequent rehydration of similarly grafted cyclic brushes allowthe full recovery of individually dispersed NPs.Although linear ligands are densely grafted onto Fe 3 O 4 cores,asmall plasma protein such as bovine serum albumin (BSA) still physisorbs within their shells.I nc ontrast, the impenetrable entropic shield provided by cyclic brushes efficiently prevents nonspecific interaction with proteins.

Robust and Biocompatible Functionalization of ZnS Nanoparticles by Catechol-Bearing Poly(2-methyl-2-oxazoline)s

“…The amount of bound polymer measured by TGA could be used to estimate the surface density of PMOXA ligands, which was always included between 2 chains nm −2 and 6 chains nm −2 , in accordance to the values previously reported for chemically similar polymer shells on metal oxide NPs. 36 The stability of ZnS-PMOXA NPs dispersions was subsequently monitored in water and in PBS at pH 7.4 by DLS (see Table 2), recording the average hydrodynamic diameter (HD) of the dispersed NPs over a period of 7 days (see Figure S11 in the Supporting Information).…”

Polymer Topology Determines the Formation of Protein Corona on Core–Shell Nanoparticles

“…C-PEOXA was polymerized as previously described and functionalized with nitrodopamine. 15 , 36 First, the linear precursor α-propargyl-ω-azido PEOXA was obtained using propargyl p -toluenesulfonate as an initiator and 2-azidoethylamine as the terminator agent. Intramolecular cyclization of α-propargyl-ω-azido PEOXA was performed by Cu-catalyzed Huisgen cycloaddition in water.…”

“… 12 Thus, in practical applications, the by far dominating strategy to achieve long-term stability in biofluids or circulation times in vivo has been to form thick, highly hydrated, and densely grafted polymer shells, so-called “polymer brush” shells. 13 − 15 A recent perspective article summarizing lessons learned by a decade of research on the NP protein corona by Caruso et al suggested that, while grafting of hydrophilic polymers to nanoparticles is the leading strategy to create “stealth” particles, their interactions are convoluted with those of the core, and their architecture can influence protein adsorption and vice versa . 16 …”

“…In contrast, cyclic polymer adsorbates feature smaller molecular dimensions with respect to their linear analogues of comparable molar mass, due to the steric constraints introduced during cyclization, 26 , 27 and thus they are capable of assembling on macroscopic and high-aspect-ratio surfaces, yielding much denser and more compact brushes. 15 , 28 Especially when applied on inorganic NPs, we recently demonstrated that cyclic PAOXA adsorbates generate an ultradense brush shell, which can substantially improve colloidal stability, also within protein dispersions. 15 …”

“… 15 , 28 Especially when applied on inorganic NPs, we recently demonstrated that cyclic PAOXA adsorbates generate an ultradense brush shell, which can substantially improve colloidal stability, also within protein dispersions. 15 …”