Core Shell Corona Research Articles

Synthesis of Platinum(II)-Containing Block Copolymers: Luminescence Enhancement and Controllable Self-Assembly.

In this work, a novel class of diblock polymer ligands, poly(ethylene oxide)-block-polystyrenes end-functionalized with 2,6-bis(benzimidazol-2'-yl)pyridine (bzimpy), have been synthesized and their coordination reactions with K2PtCl4 have created platinum(II)-containing diblock copolymers. They emit red phosphorescence in both THF-water and 1,4-dioxane-n-hexane mixed solvents, arising from Pt(II)···Pt(II) and/or π-π stacking interactions between the planar [Pt(bzimpy)Cl]+ units. Correspondingly, the block copolymers demonstrate a solvent-tunable self-assembly behavior to controllably generate vesicles and worms with core-shell-corona architectures. In these hierarchical nanostructures, the planar [Pt(bzimpy)Cl]+ blocks are associated together to form cores driven by Pt(II)···Pt(II) and/or π-π stacking interactions. Such cores are completely isolated by PS shells, which are further encapsulated by PEO coronas. It should be highlighted here that diblock polymers as polymeric ligands are coupled with phosphorescence platinum(II) complexes, representing a novel approach to create functional metal-containing polymer materials with hierarchical architectures.

Polymerization-Induced Hierarchical Self-Assembly: From Monomer to Complex Colloidal Molecules and Beyond.

The nanoscale hierarchical design that draws inspiration from nature's biomaterials allows the enhancement of material performance and enables multifarious applications. Self-assembly of block copolymers represents one of these artificial techniques that provide an elegant bottom-up strategy for the synthesis of soft colloidal hierarchies. Fast-growing polymerization-induced self-assembly (PISA) renders a one-step process for the polymer synthesis and in situ self-assembly at high concentrations. Nevertheless, it is exceedingly challenging for the fabrication of hierarchical colloids via aqueous PISA, simply because most monomers produce kinetically trapped spheres except for a few PISA-suitable monomers. We demonstrate here a sequential one-pot synthesis of hierarchically self-assembled polymer colloids with diverse morphologies via aqueous PISA that overcomes the limitation. Complex formation of water-immiscible monomers with cyclodextrin via "host-guest" inclusion, followed by sequential aqueous polymerization, provides a linear triblock terpolymer that can in situ self-assemble into hierarchical nanostructures. To access polymer colloids with different morphologies, three types of linear triblock terpolymers were synthesized through this methodology, which allows the preparation of AXn-type colloidal molecules (CMs), core-shell-corona micelles, and raspberry-like nanoparticles. Furthermore, the phase separations between polymer blocks in nanostructures were revealed by transmission electron microscopy and atomic force microscopy-infrared spectroscopy. The proposed mechanism explained how the interfacial tensions and glass transition temperatures of the core-forming blocks affect the morphologies. Overall, this study provides a scalable method of the production of CMs and other hierarchical structures. It can be applied to different block copolymer formulations to enrich the complexity of morphology and enable diverse functions of nano-objects.

Stimuli-responsive multifunctional micelles of ABC vs. ACB triblock terpolymers using reversible covalent bonding of phenylboronic acid: controlled synthesis, self-assembly and model drug release

We report the synthesis and self-assembly of well-defined, amphiphilic, biodegradable and glucose- and pH-responsive ABC and ACB triblock terpolymer multifunctional micelles in aqueous media using blocks consisting of poly(ethylene oxide) (PEO), poly(ε-caprolactone) (PCL), and boronic acid-functionalised poly(ε-caprolactone) (PBA). The terpolymers were synthesized by sequential ring–opening polymerisation (ROP) and functionalised using phenylboronic acid pinacolate via alkyne − azide cycloaddition (CuAAC). Lastly, the pinacole groups were deprotected by mild acidic catalysis to introduce phenylboronic acid for controlled drug solubilisation and delivery. ABC and ACB triblock terpolymers self-assembled into various multifunctional micelles in aqueous media depending on the state of the phenylboronic acid (pinacol protected, BAPin vs. deprotected, BA) and on the preparation procedure, as shown by dynamic and static light scattering (DLS and SLS) and by cryogenic transmission electron microscopy (cryo-TEM). The fluorescence probe Alizarin Red S (ARS) was used as a model drug, which covalently binds to BA, and its uptake was monitored by fluorescence spectroscopy and high-performance liquid chromatography (HPLC). When adding a surplus of glucose, which competitively binds to BA, ARS was released as a function of micelle morphology (core–shell corona (ABC) vs. mixed-shell (ACB) micelles). When transferring ARS-loaded nanoparticles to phosphate buffer saline (PBS) solutions at different pH values (7.4 and 5 or 3) simulating physiological and tumour conditions, respectively, ABC micelles released ARS only at low pH, while ACB micelles released ARS in response to glucose and to both low and physiological pH values. Therefore, in this system, ABC micelles are better suited for drug delivery to tumour cells than their ACB counterparts because they retain their cargo in PBS at high glucose concentrations but release it under acidic conditions, which occur in hypoxic cancer cells, thus highlighting the potential of ABC micelles for targeted drug delivery in the context of cancer therapy.

Fabrication of PεCL-AuNP-BSA core-shell-corona nanoparticles for flexible spatiotemporal drug delivery and SERS detection.

Nanoparticles with protein coronae can be used as promising multifunctional platforms for nanomedicine due to the possibility of performing surface functionalization on protein molecules and the achievement of biomedical properties. In this research, nanoparticles (NPs) with poly(ε-caprolactone) (PεCL) cores, gold NP (AuNP) shells and BSA coronae were fabricated by a self-assembly approach. The hydrophobic PεCL cores were used to encapsulate curcumin (CUR), the AuNP shells were decorated with a Raman probe, and the protein molecules in the coronae were functionalized with folic acid (FA). The self-assembly behaviors, drug delivery and the surface-enhanced Raman scattering (SERS) effect of the hybrid NPs were investigated in this research. The sizes of the core-shell-corona NPs (CSCNPs) are dependent on the initial concentrations of PεCL and AuNPs. The CUR in CSCNPs show enzyme-triggered release properties. The added lipase or trypsin can facilitate the CUR release from the hybrid NPs. The functionalization of CSCNPs with FA can significantly improve the internalization of NPs into 4T1 tumor cells due to the overexpressed folate receptors on the cells. In addition, the SERS effect of CSCNPs can be achieved when the AuNPs are decorated with 2-naphthalenethiol. The hybrid CSCNPs can be used as a promising platform for spatiotemporal drug delivery, cell imaging, and theranostics. Based on the same CSCNP platform, flexible functions can be adjusted according to the application needs.

Metal Coordination Induces Phase Segregation in Amphipolar Arborescent Copolymers with a Core-Shell-Corona Architecture.

Arborescent copolymers with a core–shell–corona (CSC) architecture were synthesized and the topology of the molecules was challenged (constrained) through intramolecular interactions, resulting in phase separation breaking the symmetry of radial density. The inner poly(2-vinylpyridine) shell of these arborescent polystyrene-g-[poly(2-vinylpyridine)-b-polystyrene] molecules can self-assemble by binding metallic salts and acids in apolar and intermediate-polarity solvents. Upon loading with HAuCl4, the characteristics of the polymer templates govern the “loading sites” of the metal within the molecules. Unique morphologies were observed for the metal-loaded G0–G4 arborescent copolymers investigated, namely, spherical, toroidal, raspberry-like, spherical nanocage, and a new worm-in-sphere morphology. The reason for the emergence of such morphologies is the interplay among intramolecular interactions of unlike polymer segments, solvent selectivity, the entropic elasticity of the arborescent substrate, and phase segregation induced by coordination with the charged metallic species. Meanwhile, the stability of the arborescent molecules against aggregation provides intramolecular phase segregation with imposed “confined” geometry and thus leads to nonconventional morphologies. Furthermore, the size of the arborescent molecules is much smaller than that of other known particles (droplets) serving as confined geometries. Computer simulations were used to model the mesostructure of the arborescent copolymers, to demonstrate the influence of solvent selectivity, together with HAuCl4 loading, on the evolution of the morphology of the macromolecules.

Europium based coordination polyelectrolytes enable core-shell-corona micelles as luminescent probes.

Core-shell-corona (CSC) micelles have multiple layers, which can serve as separate compartments. This property allows them to combine multiple functionalities in a single nanoparticle, with obvious application potential. Here, we propose a new type of CSC micelles with an apolar core and a polyelectrolyte complex shell incorporating coordination polymers. We obtain these particles by using a poly(styrene)-b-poly(vinyl pyridine)-b-poly(ethylene oxide) (PS-b-PVP-b-PEO) triblock copolymer with quaternized PVP blocks. This polymer leads to well-defined CSC micelles with a cationic shell, which allows us to entrap anionic coordination polymers without disturbing the micellar structure. Useful properties can be imported in this way, e.g., europium (Eu)-based coordination polymers endow the CSC micelles with strong luminescence. Moreover, copper ions (Cu2+) can quench the luminescence because they disturb the Eu-ligand coordination. Upon adding sulfide ions (S2-), copper ions precipitate as CuS and the Eu-ligand bond as well as the corresponding luminescence are restored. This effect is highly specific for Cu2+ and S2-: other cations or anions hardly interfere with this "on-off-on" luminescence response towards Cu2+ and S2-, demonstrating the selectivity of these CSC micelles as detectors of copper and sulfide ions.

Synthesis of Thermosensitive Conjugated Triblock Copolymers by Sequential Click Couplings for Drug Delivery and Cell Imaging.

The elegant integration of an excellent light-emitting segment and a biorelevant signal-responsive moiety could generate advanced polymeric delivery systems with simultaneously favorable diagnostic and therapeutic functions with respect to cancer theranostics. Although polymeric delivery systems based on fluorescent polyfluorene (PF) or thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) have been extensively developed, the preparation of a ternary polymer formulation composed of a PF block, a PNIPAAm sequence, and a hydrophilic moiety remains rarely explored likely because of the difficulty in integrating different synthesis strategies for polymer synthesis. To this end, herein we reported the design and controlled synthesis of a PF- and PNIPAAm-based amphiphilic triblock copolymer, PF11-b-PNIPAAm120-b-poly(oligo(ethylene glycol) monomethyl ether methacrylate)17 (PF11-b-PNIPAAm120-b-POEGMA17), with a well-defined structure by a strategy of sequential click couplings between Suzuki-coupling-generated PF and atom-transfer radical polymerization (ATRP)-produced PNIPAAm and POEGMA. The as-prepared triblock copolymers can self-assemble into micelles with a core-shell-corona (CSC) structure that is composed of an inner hydrophobic core of the PF moiety for fluorescent tracking and drug encapsulation, a thermosensitive middle shell of PNIPAAm block for thermomodulated drug loading and release, and a hydrophilic outer corona of the POEGMA segment for micelle stabilization. Interestingly, the doxorubicin (DOX)-loaded micelles prepared at 25 °C had a greater drug loading capacity than the analogues fabricated at 37 °C due to the better stability of the former formulation, leading to its higher in vitro cytotoxicity in HeLa cells. Together with the integration of a localized hyperthermia-triggered drug release profile and efficiently intracellular trafficking of the nanocarriers by monitoring the fluorescence of the PF moiety, this formulation demonstrates a great potential for cancer theranostics.

Computer simulation study on the self-assembly of tethered nanoparticles with tunable shapes.

We built a tethered nanoparticle (TNP) model that is composed of a nanoparticle with a hydrophobic tethered polymer chain. The shape of the nanoparticle can be tuned from a pure rigid cube to a soft sphere, mimicking the increase of grafting density on the nanocube surfaces. With this model, we study the self-assembly of TNPs in dilute solution using a dissipative particle dynamics simulation technique, and especially focus on the influence of particle shape, tethered chain length, and grafting density on the self-assembly structures. Some intriguing aggregates such as spherical micelles, pearl-necklace-like structures, cubic columnar structures, handshake structures, core–shell–corona micelles, and four-patch micelles have been observed when varying the interactions between cubes and solvents and the lengths of tethered chain. Modifying the nanocube surface with some hydrophilic grafted chains helps the TNPs form small micelles. Increased steric repulsion due to chain overlapping at larger grafting densities results in shape transformation of the nanoparticle from a rigid cube to a soft sphere. In these cases, the self-assembled structures are characterized by the packing of nanoparticles on the micelle surface, and the typical packing mode turns from rectangular (typical for cubes) to hexagonal (typical for spheres).

Self-Assembly of Thermosensitive Amphiphilic Pentablock Terpolymer PNIPAMx-b-PtBA90-b-PPO36-b-PtBA90-b-PNIPAMx in Dilute Aqueous Solution

A series of linear thermosensitive amphiphilic pentablock terpolymers PNIPAMx-b-PtBA90-b-PPO36-b-PtBA90-b-PNIPAMx (NxT90O36T90Nx) with various lengths x of PNIPAM block (x = 111, 107, 95, 58, 33, a...

Core-Shell-Corona Micelles from a Polyether-Based Triblock Terpolymer: Investigation of the pH-Dependent Micellar Structure.

Core-shell-corona micelles featuring a pH-responsive shell have been characterized in dilute aqueous solution at different pH values (4-8) by using dynamic light scattering (DLS), field-flow fractionation coupled with multiangle light scattering detector (FFF-MALS), steady-state fluorescence, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). The micelles are formed by self-assembly of a polyether-based triblock terpolymer consisting of a hydrophobic poly( tert-butyl glycidyl ether) block (P tBGE), a pH-responsive modified poly(allyl glycidyl ether) segment (PAGECOOH), and a neutral hydrophilic poly(ethylene oxide) block (PEO). Because of the side-chain carboxylic acids in the middle block, the micellar structure and size depends on the solution pH. Hereby, we show that an increase in pH induces a decrease in the aggregation number ( Nagg). In addition, the combination of the above measurements revealed an unexpected morphological change from spherical to ellipsoidal micelles by increasing pH.

Fabrication of Reduction-Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release.

The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core-shell-corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.

Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiram via core-shell-corona nanoparticles.

Combination therapy with different functional chemotherapeutic agents based on nano-drug delivery systems is an effective strategy for the treatment of breast cancer. However, co-delivery of drug molecules with different physicochemical properties still remains a challenge. In this study, an amphiphilic poly (ε-caprolactone)-b-poly (l-glutamic acid)-g-methoxy poly (ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer was designed and synthesized to develop a nanocarrier for the co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic disulfiram (DSF). The amphiphilic copolymer self-assembled into core-shell-corona structured nanoparticles with the hydrophobic PCL core for DSF loading (hydrophobic interaction) and anionic poly (glutamic acid) shell for DOX loading (electrostatic interaction). DSF and DOX co-loaded nanoparticles (Co-NPs) resulted in high drug loading and precisely controlled DSF/DOX ratio via formulation optimization. Compared with free drug solutions, DSF and DOX delivered by the Co-NPs were found to have improved intracellular accumulation. Results of cytotoxicity assays showed that DSF/DOX delivered at the weight ratio of 0.5 and 1 could achieve a synergistic cytotoxic effect on breast cancer cell lines (MCF-7 and MDA-MB-231). In vivo imaging confirmed that the core-shell-corona nanoparticles could efficiently accumulate in tumors. In vivo anti-tumor effect results indicated that Co-NPs showed an improved drug synergistic effect on antitumor activity compared with the free drug combination. Therefore, it can be concluded that core-shell-corona nanoparticles prepared by PCL-b-PGlu-g-mPEG could be a promising co-delivery system for drug combination therapy in the treatment of breast cancer.

Core-Shell-Corona Silica Hybrid Nanoparticles Templated by Spherical Polyelectrolyte Brushes: A Study by Small Angle X-ray Scattering.

Core-shell-corona silica/polymer hybrid nanoparticles with narrow size distribution were prepared in the template of spherical polyelectrolyte brushes (SPB) which consist of a solid polystyrene (PS) core densely grafted with linear poly(acrylic acid) (PAA) chains. The microstructure of obtained hybrid nanoparticles was studied by small-angle X-ray scattering (SAXS) and in combination with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The generation of silica shell within the brush is confirmed by the significant increase of the electron density in the shell, and the silica shell showed a unique inner-loose-outer-dense structure, whose thickness is pH sensitive but is insensitive to ionic strength as revealed by fitting SAXS data. After dissolving the PS core, hollow silica nanoparticles were obtained and determined by SAXS, which should be ideal carriers for pH-triggered drug delivery. SAXS is confirmed to be a powerful method to characterize the core-shell-corona silica/polymer hybrid and hollow silica nanoparticles.

Synthesis of Dynamic-Covalent Shell Crosslinkable Core–Shell-Corona Nanoparticles with Boronic Ester Linkages: A Potential Carrier for Drug Delivery

Synthesis of Dynamic-Covalent Shell Crosslinkable Core–Shell-Corona Nanoparticles with Boronic Ester Linkages: A Potential Carrier for Drug Delivery

Trifunctional Fe3O4/CaP/Alginate Core-Shell-Corona Nanoparticles for Magnetically Guided, pH-Responsive, and Chemically Targeted Chemotherapy.

Chemotherapy of bladder cancer has limited efficacy because of the short retention time of drugs in the bladder during therapy. In this research, nanoparticles (NPs) with a new core/shell/corona nanostructure have been synthesized, consisting of iron oxide (Fe3O4) as the core to providing magnetic properties, drug (doxorubicin) loaded calcium phosphate (CaP) as the shell for pH-responsive release, and arginylglycylaspartic acid (RGD)-containing peptide functionalized alginate as the corona for cell targeting (with the composite denoted as RGD-Fe3O4/CaP/Alg NPs). We have optimized the reaction conditions to obtain RGD-Fe3O4/CaP/Alg NPs with high biocompatibility and suitable particle size, surface functionality, and drug loading/release behavior. The results indicate that the RGD-Fe3O4/CaP/Alg NPs exhibit enhanced chemotherapy efficacy toward T24 bladder cancer cells, owing to successful magnetic guidance, pH-responsive release, and improved cellular uptake, which give these NPs great potential as therapeutic agents for future in vivo drug delivery systems.

Micellization of pH‐sensitive poly(butadiene)‐block‐poly(2 vinylpyridine)‐block‐poly(ethylene oxide) triblock copolymers: Complex formation with anionic surfactants

ABSTRACTThe micellization of three tailor‐made triblock copolymers, such as PB100–P2VP100–PEO104, PB185–P2VP108–PEO154, and PB37–P2VP115–PEO241, having similar total molecular weights and constant poly(2‐vinylpyridine) (P2VP) sequence lengths, was investigated as a function of pH and sodium dodecyl sulfate (SDS) concentration. At pH 7 the formation of intermicellar aggregates was observed, especially for copolymers of low poly(ethylene oxide) (PEO) content. A pH decrease from 7 to 3 leads to a particle size increase due to the electrostatic repulsion of the protonated P2VP chains. The influence of the PEO sequence length was also observed for zeta potential values. At pH 3, in the absence of SDS, core–shell–corona micelles are formed whereas in the presence of small amount of SDS (degree of neutralization DN = 0%–50%), a complex is formed between SDS and the protonated P2VP which leads to the shrinkage of the shell and thus to a decrease of the micellar sizes. For higher DN values, the micellar sizes increase due to the formation of large agglomerates and a transition occurs from a monomodal to a bimodal size distribution. Furthermore, it turned out that secondary aggregation, such as intermicellar aggregation, can completely be avoided if the degree of polymerization (DPn) of the water‐soluble block is significantly higher than the DPn of the water‐insoluble sequence. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45313.

Nitroxide-Mediated Polymerization-Induced Self-Assembly of Block Copolymers at the Surface of Silica Particles: Toward New Hybrid Morphologies

Silica/polymer latexes with concentric core–shell–corona, half-capped, snowman-like vesicular, tadpole- and centipede-like morphologies have been produced by nitroxide-mediated polymerization-induced self-assembly (PISA) performed in the presence of aqueous suspensions of colloidal silica. A hydrosoluble brush-like PEO-based macroalkoxyamine (P[(poly(ethylene oxide) methyl ether methacrylate)12-co-styrene]-SG1, Mn = 11 700 g mol–1 and Mw/Mn = 1.11) was first adsorbed onto the surface of submicronic silica particles. The obtained suspension was then used in the emulsion polymerization of n-butyl methacrylate with 8 mol % of styrene. This led to the formation of amphiphilic block copolymers (BCPs) that self-assembled in situ at the silica surface into well-defined hybrid nano-objects of various morphologies, in agreement with the principles of polymerization-induced micellization. The influence of the pH was more specifically investigated, using silica particles of different size ranging from 30 to 230 nm. ...

Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV–vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core–shell–corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.

Self-assembled core–shell-corona multifunctional non-viral vector with AIE property for efficient hepatocyte-targeting gene delivery

Core–shell-corona multifunctional nanoparticles were prepared and used for cell imaging and cell-targeting delivery of genes toward hepatocytes.

Temperature-induced structure switch in thermo-responsive micellar interpolyelectrolyte complexes: toward core-shell-corona and worm-like morphologies.

The spontaneous formation and thermo-responsiveness of a colloidally-stable interpolyelectrolyte complex (IPEC) based on a linear temperature-sensitive diblock copolymer poly(vinyl sulfonate)31-b-poly(N-isopropyl acrylamide)27 (PVS31-b-PNIPAM27) and a star-shaped quaternized miktoarm polymer poly(ethylene oxide)114-(poly(2-(dimethylamino)ethyl methacrylate)17)4 (PEO114-(qPDMAEMA17)4) was investigated in aqueous media at 0.3 M NaCl by means of dynamic light scattering (DLS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). The micellar macromolecular co-assemblies show a temperature-dependent size and morphology, which result from the lower critical solution temperature (LCST) behavior of the PNIPAM-blocks. Hence, the micellar co-assemblies grow upon heating. At 60 °C, spherical core-shell-corona co-assemblies are proposed with a hydrophobic PNIPAM core, a water-insoluble IPEC shell, and a hydrophilic PEO corona. These constructs develop into a rod-like structure upon extended equilibration. In turn, PEO-arms and PNIPAM-blocks within a hydrophilic mixed two-component corona surround the water-insoluble IPEC domain at 20 °C, thereby forming spherical core-corona co-assemblies. Reversibility of the structural changes is suggested by the scattering data. This contribution addresses the use of a combination of oppositely charged thermo-responsive and bis-hydrophilic star-shaped polymeric components toward IPECs of diverse morphological types.