Understanding the Temperature‐Responsive Self‐Assemblies of Amphiphilic Random Copolymers by SANS in D₂O Solution

Abstract

The self‐assembly behavior, in aqueous solution, of amphiphilic methacrylic random copolymers with perfluoroalkyl and polyoxyethylene side chains and the morphology of the resulting nanostructures are investigated by small‐angle neutron scattering (SANS). The results allow to clarify the effect of temperature on the self‐assembly features of copolymers and the structural morphology of both unimer single‐chain entities and larger multi‐chain aggregates of unimers. Shape, flexibility, and size of the aggregates are proved to be modulated by temperature and copolymer composition. The existence of three distinct phases of self‐assembled structures is pointed out as a function of increasing temperature: 1) globular unimers; 2) coexistence of extended unimers and aggregates; and 3) aggregates, which overall show full reversibility in a wide range of copolymer concentrations.

Self-Assembled Amphiphilic Fluorinated Random Copolymers for the Encapsulation and Release of the Hydrophobic Combretastatin A-4 Drug

“…In this work, we encapsulated CA-4 in two different amphiphilic random copolymers capable of self-folding into unimer micelles [20,22], composed, in one case, of tri(ethylene glycol) methyl ether methacrylate (TEGMA) and FA (TEGMA-ran-FA) and in the other case of PEGMA and FA (PEGMA-ran-FA). Both copolymers were found to display an LCST-behavior, with a cloud point temperature of 37 • C for TEGMA-ran-FA and well above the body temperature for PEGMA-ran-FA.…”

“…The inclusion of low surface energy fluoroalkyl side chains in a polymer structure is, in fact, known to drastically enhance the hydrophobic and lipophobic nature of the entire system, which results in a strong tendency to self-assemble in solution, in bulk and at the surface of thin films [15][16][17][18]. Follow-up studies by our group on similar copolymers of PEGMA and perfluorohexylethyl acrylate (FA) identified the formation of self-folded nanostructures by several complementary experimental analyses, including neutron scattering and molecular dynamics simulations, and we also studied the thermoresponsive features of the copolymers, which reversibly collapsed and aggregated into multi-chain aggregates at temperatures varying with copolymer composition [19][20][21][22].…”

“…Many of the nanoobjects obtained from the self-assembling of amphiphilic copolymers containing PEG side chains possess an LCST in aqueous solution, which can be tuned by adjusting the copolymer composition [14,22,36]. Thermoresponsive nanoscale polymeric systems possessing an LCST have seen extensive study during the last two decades as potential drug carriers.…”

Investigation of the LCST-Thermoresponsive Behavior of Novel Oligo(Ethylene Glycol)-Modified Pentafluorostyrene Homopolymers

“…In our case, the latter may have occurred by direct aggregation of self-folded unimers, or by the opening (or partial opening) of the self-folded unimers followed by their aggregation in a more extended conformation, in analogy with the thermal-induced aggregation of protein after the unfolding process [44][45][46][47]. A recent small-angle X-ray scattering (SAXS) investigation on the self-assembly behavior in aqueous solution of amphiphilic (meth)acrylic random copolymers containing perfluoroalkyl and oligo(ethylene glycol) side chains highlighted that the aggregation process can be considered an assembling of self-folded unimers in an extended (partially opened) conformation, resulting in a rod-shaped structure [48].…”

“…havior in aqueous solution of amphiphilic (meth)acrylic random copolymers containing perfluoroalkyl and oligo(ethylene glycol) side chains highlighted that the aggregation process can be considered an assembling of self-folded unimers in an extended (partially opened) conformation, resulting in a rod-shaped structure [48]. The onset (Tonset) and the maximum (Tmax) temperatures in the process are reported in Table 3.…”