Swelling of a Responsive Network within Different Constraints in Multi

Article Cite This: Macromolecules XXXX, XXX, XXX−XXX

Swelling of a Responsive Network within Different Constraints in Multi-Thermosensitive Microgels Monia Brugnoni,† Andrea Scotti,† Andrey A. Rudov,§,∥ Arjan P. H. Gelissen,† Tobias Caumanns,⊥ Aurel Radulescu,# Thomas Eckert,† Andrij Pich,§,‡ Igor I. Potemkin,§,∥,% and Walter Richtering*,† †

Institute of Physical Chemistry and ‡Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52056 Aachen, Germany § DWI - Leibniz Institute for Interactive Materials e.V., 52056 Aachen, Germany ∥ Physics Department, Lomonosov Moscow State University, 119991 Moscow, Russian Federation ⊥ GFE Central Facility for Electron Microscopy, RWTH Aachen University, 52074 Aachen, Germany # Jülich Centre for Neutron Science, Outstation at MLZ, 85748 Garching, Germany % National Research South Ural State University, 454080 Chelyabinsk, Russian Federation S Supporting Information *

ABSTRACT: We report on the swelling of a polymeric network in doubly thermoresponsive microgels. Silica-core double-shell and hollow double-shell microgels made of an inner poly(N-isopropylmethacrylamide) and an outer poly(N-isopropylacrylamide) shell are studied by exploiting the distinct temperature sensitivities of the polymers. The swelling states of the two shells can be tuned by temperature changes enabling three different swelling states: above, below, and between the distinct volume phase transition temperatures of the two polymers. This enables to investigate the effect of different constraints on the swelling of the inner network. Small-angle neutron scattering with contrast variation in combination with computer simulation discloses how the expansion of the inner shell depends on the material and swelling state of its constraints. In the presence of the stiff core, the microgels show a considerable interpenetration of the polymeric shells: the inner network expands into the outer deswollen shell. This interpenetration vanishes when the outer network is swollen. Furthermore, as predicted by our computer simulations, an appropriate choice of cross-linking density enables the generation of hollow double-shell nanocapsules. Here, the inner shell undergoes a push−pull ef fect. At high temperature, the collapsed outer shell pushes the swollen inner network into the cavity. At lower temperature, the swelling of the outer network contrary pulls the inner shell back toward the external periphery.

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INTRODUCTION

In the past decades, the improvements in the synthesis protocols for microgels, also called nanogels, have allowed to tailor precisely their structure and characteristics. This enables to investigate complex structures and to elaborate the behavior of responsive networks under different constraints. Core−shell structured microgels made of a polymeric core with higher volume phase transition temperature (VPTT) than the shell enable studying the swelling of the core in the

The swelling of polymeric networks in solvents is well-known to be controlled by various triggers as e.g. temperature, pH, salt concentration, or solvent composition.1−8 Questions regarding the compressibility and interpenetration of cross-linked polymeric microgels in various surroundings e.g. in concentrated surroundings are under strong investigation, unraveling influences of architecture and cross-linking density.9−12 Moreover, their behaviors at different interfaces show astonishing properties regarding structural changes due to compression or spreading.13−18 © XXXX American Chemical Society

Received: December 22, 2017 Revised: March 5, 2018

A

DOI: 10.1021/acs.macromol.7b02722 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

in the presence of an incompressible core. In its absence, the inner shell has the opportunity to swell into the solvent filled cavity instead of expanding into the deswollen outer shell. This leads to a decrease of the cavity size compared to the swelling state when both networks are fully deswollen. Finally, the interaction of the two contracted shells has the effect of preserving the cavity of the hollow microgels.

confinement of the shell, when the latter is deswollen (above its VPTT) or swollen (below the VPTT).19−24 The combination of a poly(N-isopropylmethacylamide) (pNIPMAM) core with a VPTT of 42−44 °C in water and a poly(N-isopropylacylamide) (pNIPAM) shell with a VPTT at 32−34 °C is an example for such a constraining system. It unraveled that at temperatures between the VPTTs a collapsed shell leads to a restriction of the core swelling in combination with an increase in polymer density.21 The use of microgels sheds light not only on the fundamental question how networks behave in confinements but also on their potential for applications in different technological fields.25 Indeed, microgels are very appealing as biosensors,26 membranes for filtration,27 insulin-releasing thin films,28 and synthetic platelet analogues.29 Furthermore, stimuli-switchable nanocarriers enable guest delivery in a controlled fashion.30−32 Multifunctional microgels made of responsive polymers reveal promising features as novel carrier systems.33,34 Here, we answer the question how a polymeric network swells within two constraints and investigate how the material making the confinements is coupled to the swelling behavior. For this purpose, core−double-shell and hollow double-shell microgels made of a stiff silica core and two distinct thermoresponsive polymeric shells, as illustrated in Figure 1,

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EXPERIMENTAL SECTION

Materials. Tetraethyl orthosilicate (TEOS), ammonia solution (28−30%), and the surfactant sodium dodecyl sulfate (SDS) were purchased from Merck. 3-Methacryloxypropyltrimethoxysilane (MPS), the monomer N-isopropylmethacrylamide (NIPMAM), and the crosslinker N,N′-methylenebis(acrylamide) (BIS) were obtained from Sigma-Aldrich. The monomer N-isopropylacrylamide (NIPAM) and the initiator potassium peroxydisulfate (KPS) were purchased from Acros Organics. Ethanol and sodium hydroxide (NaOH) were purchased from VWR. Heavy water (D2O, 99.9%) was delivered by Deutero GmbH. The polymerizations were performed in filtered (0.2 μm RC membrane filter) double-distilled Milli-Q water. Synthesis. The syntheses of core−shell and hollow microgels have been previously described using different approaches.35−40 Our procedure is based on the synthesis route of Dubbert et al.41 The silica nanoparticles serving as sacrificial cores were prepared according to the well-known Stöber synthesis.42 Briefly, 174 mL of ethanol was preheated to 60 °C. After addition of 20 mL of ammonia solution (28−32%), the solution was left to equilibrate. The reaction was initiated by rapid addition of 6 mL of TEOS and left to proceed for 24 h at 60 °C. The surface functionalization was performed by adding an excess of MPS to introduce reactive double bonds on the nanoparticle surface to ensure later attachment of the polymeric shells.7 The silica nanoparticles were purified by 3-fold centrifugation (5000 rpm) and redispersion in fresh ethanol. Subsequently, the CS microgels were synthesized by adding 225.0 mg of silica nanoparticles in 1.5 mL of ethanol to a solution of 300.5 mg of NIPMAM, 40.5 mg of BIS (10 mol%), and 14.6 mg of SDS in 47 mL of water into a three-neck round-bottom flask equipped with a KPG stirrer and a reflux condenser. The appropriate seed concentration to avoid the growth of secondary homopolymeric nuclei during the polymerization was determined by preliminary small scale syntheses (see Supporting Information, Figure S.5). The suspension was purged with nitrogen under constant stirring at 200 rpm and heated to 60 °C. An initiator solution of 21.0 mg of KPS in 3 mL of water was degassed separately. The reaction was started by rapid addition of the initiator solution through a nitrogen washed syringe into the monomer solution and left to proceed for 4 h at 60 °C under constant nitrogen flow and stirring. The resulting CS microgels were purified by three cycles of ultracentrifugation (30 000 rpm) and redispersion in fresh water. Lyophilization was performed for storage. The CSS microgels were synthesized likewise. Briefly, 60 mg of the freeze-dried CS microgels was redispersed overnight in 3 mL of water. Then, 113.2 mg of NIPAM, 8.1 mg of BIS (5 mol%), and 2.9 mg of SDS were dissolved in 6 mL of water and added to the CS dispersion. The reaction solution was degassed and heated to 60 °C, before adding the degassed initiator solution of 4.2 mg of KPS in 1 mL of water. The reaction proceeded for 4 h at 60 °C. The CSS microgels were purified and lyophilized as aforementioned. The generation of the hollow nanocapsules (HS and HSS) by dissolution of the silica cores in NaOH solution was reported previously.41 The CS and the CSS microgels were dissolved in 0.05 M NaOH solution containing 1.18 mg/mL SDS for electrostatic stabilization of the nanospheres. The dissolution was performed at 42 °C for 5 days. Dialysis against water was performed for neutralization and purification. The polymeric network of microgels is not affected by this treatment (see Figure S.6). Dynamic Light Scattering. Dynamic light scattering (DLS) was performed to determine the hydrodynamic radii, Rh, of the silica nanoparticles and the microgels. An ALV setup connected to a goniometer and a HeNe laser (λ = 633 nm) was used for all

Figure 1. Schematic representation of core−double-shell and hollow double-shell microgels with an inner pNIPMAM (green) and an outer pNIPAM (blue) shell illustrating the different confinement boundaries of the inner network. The arrows illustrate the possible expansion directions upon swelling of the distinct networks.

were investigated. The shell composition was chosen as such that the swelling of the inner shell can be investigated between either an incompressible core and a deswollen outer shell or the core and a swollen outer shell. Moreover, the core removal enables the opportunity to investigate the same shell composition in the absence of the stiff boundary, replacing it by a solvent filled cavity. For this purpose, silica-core doubleshell and the corresponding hollow microgels made of an inner pNIPMAM and an outer pNIPAM shell are investigated. We compare the temperature-dependent size of the core− single- (CS), core−double- (CSS), hollow single- (HS), and hollow double-shell (HSS) microgels determined by means of multi-angle dynamic light scattering. Cryogenic transmission electron microscopy was chosen as visualization method to gain first structural information on the hollow nanocapsules. Smallangle neutron scattering with contrast matching was used to investigate the effects of swelling and deswelling of the distinct shells on the internal structure of both core-containing and hollow microgels. The form factors of all presented microgels were probed at temperatures above, between, and below the VPTTs of the two polymers. Our experimental findings show that the swelling of the inner shell leads to interpenetration into the collapsed outer network B


Article

Macromolecules measurements. A programmable thermostat was employed to adjust the temperature of the toluene bath surrounding the sample under investigation. For each temperature, a minimum of 10 different angles, with an acquisition time of 60 s, was measured. The average diffusion coefficient, D0, of the particles in solution was determined by linear regression of the decay rate, Γ , from the second-order cumulant fit as a function of the magnitude of the scattering vector q, with Γ = q2D0.43 The samples were highly diluted to prevent both multiple scattering and interparticle interactions. The microgels were investigated in the same solvent used for small-angle neutron scattering: The hollow gels were probed in pure D2O and the core-containing microgels in a 62 wt% D2O/H2O mixture (see below). The hydrodynamic radii were determined by means of the Stokes−Einstein equation, and the errors are obtained from error propagation.44 Cryogenic Transmission Electron Microscopy. Cryogenic transmission electron microscopy (Cryo-TEM) was used to visualize the hollow microgels. A Carl Zeiss Libra 120 microscope operating at a voltage of 120 kV with a bottom mounted CCD camera was employed to observe the zero-loss energy-filtered transmission electron microscopy images. The samples were prepared by rapid vitrification in liquid ethane from an aqueous dispersion of microgels. 4 μL of preheated dispersion was transferred in a vitrobot system set to the desired temperature at 100% humidity onto a Lacey carbon coated TEM grid. The grid was hydrophilized in an air plasma oven for 90 s before use. The CS and CSS microgels were not investigated due to poor shell contrasts in comparison to the silica core. A visualization of the intermediate swelling degree (34 °C < T < 44 °C) with a swollen inner and a collapsed outer shell is not shown. The vitrification setup precludes an exact temperature control which is crucial to investigate this swelling state. Small-Angle Neutron Scattering. Small-angle neutron scattering (SANS) experiments were performed at the KWS-2 by Jülich Centre for Neutron Science (JCNS) at the Heinz Maier-Leibnitz Institute in Garching, Munich. The q-range of interest was covered using three configurations: sample−detector distance, dSD = 20 m with neutron wavelength λ = 10 Å, dSD = 8 m with λ = 5 Å, and dSD = 2 m with λ = 5 Å. The instrument is equipped with a 3He detector, and the wavelength resolution was Δλ/λ = 20%. The concentration of all samples was 2 mg/mL. Thus, the structure factor can be approximated to one, and the scattered intensity, I(q), is proportional to the form factor of the suspended microgels, P(q). The latter contains information on the internal geometry of the scattering objects. The HS and HSS nanocapsules were measured at full contrast in D2O. The CS and CSS microgels were measured in a 62 wt% D2O in H2O mixture which corresponds to the match point of the silica core (ρSilica = 3.469 × 10−6 Å−2).40 This is necessary to probe the polymeric shells as the silica cores are denser and have a higher scattering contribution than the polymer. All scattering curves were corrected by background subtraction as well as empty cell scattering and dark count rate. After data reduction, the scattering curves of the CS and CSS microgels are indistinguishable from the background for q ≳ 0.18 nm−1 because of higher incoherent scattering of the D2O/H2O mixture. To fit the acquired scattered intensities and obtain structural information, we used the core−multi-shell model proposed by Schmid et al.34 The model was adapted to a double-shell system to distinguish between the polymer volume fractions of the distinct shells. Δρsh,in and Δρsh,out represent the differences between the scattering length density of the solvent and the inner (sh,in) or the outer shell (sh,out). Wsh,in, Wsh,out, Vsh,in, and Vsh,out describe the widths and the partial volumes of the two shells. Δρcore is the difference between the scattering length density of the solvent and the core. The model describes a structure with an interpenetrating layer of core and inner shell of the length 2σin, a intermediate interpenetration layer between the shells 2σint, and a fuzzy outer surface with an extension σout. The scattering amplitude for core−double-shell microgels is given by

A(q) = Δρsh,out Vsh,out Φsh,out(q , R sh,out , σout) + (Δρsh,in − Δρsh,out ) Vsh,in Φsh,in(q , R sh,in , σint) + (Δρcore − Δρsh,in )Vcore Φcore(q , R in , σin)

(1)

with Rsh,in = Wcore + 2σin + Wsh,in + σint and Rsh,out = Wcore + 2σin + Wsh,in + 2σint + Wsh,out + σout. Φ(q,R,σ) represents the normalized Fourier transform of the radial density profile

Φ(q , R , σ ) = × +

1 ⎡⎛ R 1 ⎞ cos[q(R + σ )] ⎛ R 1⎞ ⎢⎜ + ⎟ +⎜ 2 − ⎟ 4 ⎝ ⎠ σ σ⎠ Vn ⎣⎝ σ 2 q σ

cos[q(R − σ )] q

4

−

3 sin[q(R − σ )] 5 2

qσ

−

2R cos(qR )

6 sin(qR ) ⎤ ⎥ q5σ 2 ⎦ 3

q 4σ 2

(2) 2

21 a

where Vn = R /3 + Rσ /6. The form factor is proportional to the squared scattering length amplitude

P(q) ∝ A2 (q)

(3)

To account for the scattering at high q-values relying on the inhomogeneities in the polymer network due to the cross-linking, a Lorentzian term is added to the fitting models: Ichain(0)/(1 + q2ξ2), where Ichain(0) is the value of the scattered intensity due to the chain at q = 0 and ξ the average mesh size of the two polymeric network.45,46 We used an average value for ξ instead than two distinct for the 5 and 10 mol% cross-linked networks. This is linked on one hand to the fact that such a small difference in the cross-linking density has only small effects on ξ9,45,47,48 and on the other hand to not biasing the fit results with redundant parameters.49 A constant background is added to account for the incoherent scattering. Finally, the model is convoluted with a resolution function to account for the smearing due to the instrument.50 The silica cores of the microgels under investigation are either contrast matched (CS and CSS) or not present (HS and HSS): Thus, the contrast of the core, Δρcore, is equal to 0 for all form factors presented here.

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COMPUTER SIMULATIONS Brownian molecular dynamics (MD) simulations within a standard coarse-grained model with implicit solvent were performed at the supercomputer JURECA, Jülich Supercomputing Centre. The LAMMPS package was used.51 Without loss of generality, the simulations were carried out using dimensionless units, where the fundamental quantities such as mass m, diameter of the bead σ, and the Boltzmann constant kB are considered to be equal to 1. All beads of the microgels (including monomer units, cross-links, and beads of the solid core) were modeled as Lennard-Jones particles. The connectivity of the beads into a polymer network was maintained by the finite extension nonlinear elastic (FENE) potential:52 ⎛ 1 r2 ⎞ UFENE(r ) = − KR max 2 ln⎜1 − 2 ⎟ 2 R max ⎠ ⎝

(4)

2

where the spring constant K = 30kBT/σ and the maximum bond length Rmax = 1.5σ. The distance between two beads is denoted by r. The repulsive part of the bond potential was represented by the Lennard-Jones potential ⎡⎛ σ ⎞12 ⎛ σ ⎞6 ⎤ Ubond(r ) = 4εbond⎢⎜ ⎟ − ⎜ ⎟ ⎥ + εbond ⎝r⎠ ⎦ ⎣⎝ r ⎠ C

(5)


Article

Macromolecules with εbond = 1kBT and cutoff radius rcut = 21/6σ. The solvent quality for the microgel shells is quantified by the interaction parameters ε1 and ε2 in the Lennard-Jones potentials (see below). The microgels were designed in a similar way as reported before by Richtering et al. with certain modifications.33 Briefly, we used an ideal diamond cubic crystal structure for the preparation of the solid nanoparticle (core). The spherical shape of the core was provided via inscribing a sphere of an appropriate radius into the cubic crystal (15 × 15 × 15 unit cells) and cropping all the beads which are outside this sphere. We also used the ideal diamond cubic crystal structure (9 × 9 × 9 unit cells) to prepare a network (gel). In this structure, the edges represent fully stretched subchains which are connected with each other by tetrafunctional cross-links. Spherical network layers were obtained via inscribing two spheres of different radii into the cubic crystal and cropping the beads which are outside the outer sphere and inside the inner sphere. To get the HSS microgel with different cross-linking density in the shells, two network layers of different dimensions were designed and then cross-linked with each other through the dangling chains. The CSS microgel is prepared using HSS via filling the cavity with the core and further cross-linking to the inner shell. The number of beads in each subchain in the inner shell was chosen to be 10 (4) which corresponds to the case of approximately 5% (10%) of cross-links. Considering that 4 halves of the subchains account for each tetrafunctional cross-linker, the estimated fractions of the cross-links are 1/(4 × 5 + 1) ≈ 0.047 and 1/(4 × 2 + 1) ≈ 0.11. In the outer shell, the number of beads in each subchain is equal to 10, which corresponds to the case of 5% cross-linking density. The radii of the core, the inner and the outer shells were selected in such a way that the numbers of the beads (masses) corresponded to the ratio 0.15:0.48:0.37, respectively. The interactions between any pair of the beads were described through the truncated-shifted Lennard-Jones potential.53 The values of the dimensionless Lennard-Jones interaction parameters ε1, ε2, and ε12 = (ε1ε2)1/2, describing bead−bead interactions in the inner (ε1) and outer (ε2) shells as well as between the shells (ε12), were varied between 0.1kBT and 1kBT corresponding to the repulsion in good solvent and attraction in poor solvent, respectively. Attraction of the beads in the solid core was described by the interaction parameter ε0 = 0.33kBT, which implies that the solvent is poor for the nanoparticles. After fixing the primary structures of the microgels, they were placed in a cubic simulation box of the volume V = 5003 σ3 with periodic boundary conditions and subjected to annealing at different values of ε1 and ε2. The calculations were carried out in a NVT ensemble, which is quite efficient for models with implicit solvent.54,55 They last 50 × 106 simulation steps, which is enough to approach the equilibrium states of the systems.56,57

Therefore, microgels with different amounts of cross-links in the inner but constant cross-links in the outer shell were simulated. Especially at intermediate swelling, with swollen inner (ε1 = 0.1kBT) and deswollen outer (ε2 = 1kBT) shell, we assume that the polymer shell is likely to swell into the cavity leading to a disappearance of the hollow structure. Figure 2

Figure 2. Cross section through the center of mass of core−doubleshell (left semicircle) and hollow double-shell (right semicircle) microgels with a swollen inner (ε1 = 0.1kBT) and a deswollen outer (ε2 = 1kBT) shell with (left) 5% cross-links in the inner and outer shell and (right) 10% cross-links in the inner and 5% in the outer network.

compares the equilibrium structures of core−double-shell and hollow double-shell microgels with different cross-linking densities in the inner network. All other swelling states (fully swollen and fully deswollen) are shown in the Supporting Information (see Figures S.1 and S.3). The equilibrium structure of a microgel made of a 5% crosslinked inner and outer shell at the state with a swollen inner (gray) and a deswollen outer shell (green) in the presence (left semicircle) and absence (right semicircle) of a stiff incompressible core (orange) is shown in Figure 2 (left). The corresponding density profiles are shown in the Supporting Information (see Figure S.2). The relatively loosely cross-linked inner network swells into the void. Thus, an apparent cavity cannot be maintained when the core is removed from the microgel. In addition, the outer shell does not collapse to an intact shell but forms a patchy surface. This has been observed for different microgel architectures before.24,58 As we are aiming to investigate the swelling of the internal network under confinement, an intact and compact external shell is strongly required. In contrast, Figure 2 (right) depicts the structure of a 10% cross-linked inner shell surrounded by a 5% cross-linked outer network. Here, the core−double-shell structure is comparable to the gels with the looser cross-linked inner shell. However, the difference in the hollow microgels is crucial: The network is able to maintain a cavity of the size comparable to the initial core size. The radial profiles of this microgel are illustrated and discussed below (see Figure 5). It can be concluded that a high cross-linking density in the inner shell is necessary to maintain the cavity under expansion of the inner shell while the outer one is deswollen. This motivates our choice of cross-linking content for the synthesis of the core−double-shell microgels. The microgels presented below were synthesized by means of a sacrificial silica core with a hydrodynamic radius of Rh = 81 ± 1 nm. The characterization of the bare cores is summarized in the Supporting Information (see Figure S.4).

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RESULTS AND DISCUSSION Previous studies indicate that the amount of cross-links in the shell of hollow microgels is significant to sustain the hollow structure independently on the swelling state.40 To avoid the syntheses of microgels with various cross-linking contents, we predict the persistence of a cavity in hollow pNIPMAM− pNIPAM double-shell microgels by computer simulations. Preliminary MD simulations were performed to make forecasts on the internal structure. We suspect that the hollow structure is strongly dependent on the architecture of the inner shell. D


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Figure 3. (A) Temperature-dependent hydrodynamic radii of the CS (black squares) and CSS (red circles) microgels in a 62 wt% D2O/H2O mixture probed by DLS. The blue line represents the size of the bare silica cores. (B) Thermoresponsiveness of the HS (black hollow squares) and HSS (red hollow circles) nanocapsules in D2O.

At temperatures below the VPTT of the pNIPAM network (T < 34 °C) both shells are swollen leading to overall radii larger than the bare CS gels. A similar restrictive behavior was observed for fully polymeric core−shell microgels, with a swollen polymeric core and a deswollen shell.21 This restriction is commonly known as Corset ef fect. The main difference of our system is the presence of the incompressible silica core in the center of the microgel which acts as confinement boundary. Further stucture determination is necessary to understand the interplay of the polymeric shells. After removal of the rigid core, we expect the network not only to expand toward the external periphery: The solvent filled cavity allows the polymeric shell to swell to the interior of the microgels. Figure 3B illustrates the thermoresponsivenesses of the HS and HSS nanocapsules in pure D2O. The HS (black hollow squares) microgels show a VPTT of 44 °C, and upon cooling, the overall radius increases from 140 to 220 nm. The HSS (red hollow circles) capsules present two distinct VPTTs, corresponding to the VPTT of pNIPAM and pNIPMAM. The swelling behaviors of both hollow microgels are similar to the precursory CS and CSS gels. The absolute sizes, determined in pure H2O, unravel that the hollow microgels are systematically larger than the corecontaining microgels (see Figure S.7). This increase of the radius is apparently related to the core removal procedure: The attachment to the silica core limits the swelling of the network. After dissolution, the shells gain the ability to expand more freely without internal restriction of the core. To conclude, DLS indicates an expansion of the pNIPMAM shell when the outer pNIPAM network is still deswollen in presence and absence of the silica core. Cryo-TEM was chosen to get first insights into the internal structure of the hollow microgels and verify the core removal. It was employed to visualize the HSS nanocapsules vitrified in the fully deswollen state at 50 °C (Figure 4A) and in the fully swollen state at 20 °C (Figure 4B). The micrographs of the HS microgels (see Figure S.8) show smaller radii in the swollen state compared to the HSS nanocapsules. This confirms the successful generation of the second pNIPAM shell. Above the VPTT (Figure 4A), the HSS capsules show smaller radii than at 20 °C (Figure 4B). This indicates a successful vitrification in the deswollen state. A core−shell

Two spatially separated pNIPMAM and pNIPAM shells were synthesized in two sequent synthesis steps. A 10 mol% crosslinked pNIPMAM shell is polymerized on the silica cores to produce core−shell (CS) microgels. After addition of the 5 mol% cross-linked pNIPAM shell core−double-shell (CSS) microgels are obtained. The hollow single- (HS) and doubleshell (HSS) microgels are generated by core dissolution. In the following, we present the temperature-dependent size determined by DLS analysis of all microgels. It is well-known that water and heavy water do not only show different scattering length densities ideal for SANS but have also different impacts on the swelling of polymeric networks.59 Thus, we investigate the swelling behavior of all microgels in pure H2O to compare the absolute sizes (see Figure S.7). In addition, we studied the swelling of the microgels in the solvents required for contrast matching in SANS for convenient comparison of the same swelling states. Figure 3A shows the hydrodynamic radii, Rh, of the CS (black squares) and CSS (red circles) microgels in dependence of temperature in the D2O/H2O mixture. The temperatureindependent size of the silica core is depicted by the continuous line. The CS microgels show a VPTT at 44 °C as commonly known for pNIPMAM.21 The shell has a thickness of 45 nm in the collapsed state (T > 44 °C) which can swell up to 120 nm. This relatively low swelling capability is related to the high cross-linking density. The addition of the outer pNIPAM shell results in CSS microgels with two distinct VPTTs. The overall size in the fully collapse state (T > 44 °C) indicates a successful synthesis of the outer shell with a thickness of 19 nm. At temperatures between the two VPTTs (34 °C < T < 44 °C), the solvent quality is good for the inner pNIPMAM network and bad for the outer pNIPAM network. The total radius slightly increases compared to the fully deswollen state. However, the CSS microgels are considerably smaller than the CS gels. This leads to the hypothesis that the inner pNIPMAM shell cannot swell to its maximum and expands only partially. The deswollen outer pNIPAM shell is able to strongly restrict the swelling of the inner network. E


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of the size comparable to the preliminary silica core and it is maintained at all swelling degrees. This is in agreement with previous studies.41 The scattering curves corresponding to the form factors of the double-shell microgels are shown in Figures 5A and 5B. The relative polymer volume fractions resulting from form factor analysis are illustrated in dependence of the radial distance from the center of the microgels at different temperatures (Figures 5C and 5D). The radial distances are normalized with respect to the fully swollen state to facilitate the comparison of experimental data with the simulated couterparts (Figures 5E and 5F). The absolute radii are stated in the Supporting Information (see Table S.1). The total radii of the microgels obtained from SANS form factor analysis are consistent for all temperatures with the hydrodynamic radii determined by DLS. The latter are as expected systematically larger (of some nanometers). This is related to the fact that SANS is less sensitive to the dangling chains with low polymeric density located at the periphery of the microgels.9,40,41,45,62 The relative polymer volume fractions are rescaled, supposing that the polymer mass is conserved at all swelling states and does not change after core removal. The volume fractions of all double-shell microgels are normalized with respect to the profiles of the fully collapsed CSS microgels (50 °C or ε1 = ε2 = 1kBT). In general, the computer simulations are in good agreement with our experimental findings. Hence, they are discussed collectively. For the CSS microgels (Figures 5C and E), all radial profiles unravel a temperature-independent core radius. The shells show no fuzziness toward the interior which has been observed as well for the CS microgels. Since the silica cores are matched with the solvent, they do not contribute to the scattering; in gray we mark the area occupied by the core. The profiles clearly depict the presence of a rigid core. In both methods, SANS and simulations, the CSS microgels show two fully collapsed shells accompanied by no fuzziness at the peripheries in bad solvent (red lines). At intermediate swelling (green dashed-dotted lines), we expect the inner pNIPMAM network to expand while the outer pNIPAM shell remains deswollen. This is confirmed by the radial profiles. The inner shell shows a strong decrease in the relative volume fraction due to solvent uptake accompanied by an increase of the total size of the microgel. An interesting effect is observed in the SANS profile: The value of the relative volume fraction of the pNIPAM shell is greater than 1. This means that there is more polymer present in the outer shell than at 50 °C. The presence of the stiff silica core prevents the expanding pNIPMAM network to swell toward the interior of the microgel. As a result, the inner network penetrates into the collapsed, but permeable outer shell. Thus, shell interpenetration occurs. This is not observed in the profiles obtained from simulation. The difference is probably related to the neglect of the inhomogeneous distribution of the cross-links in our model: inhomogeneous cross-linked microgels show distinct swelling behavior.63 Finally, at full swelling (blue dashed lines), both polymeric shells are fully swollen with a fuzzy periphery arising from an inhomogeneous distribution of the cross-links in the shells. This leads to free dangling chains at the surface of the microgels with low polymer density.45,64 The shells are distinguishable as the inner pNIPMAM shell has a higher polymer concentration

Figure 4. Cryo-TEM micrographs of the HSS microgels vitrified at (A) 50 °C and (B) 20 °C. Scale bars: 500 nm.

structure can be distinguished, but a hollow structure cannot clearly be identified, as the contrast of the core is not obviously lower than of the shell. Moreover, the two polymeric shells are not distinguishable, as they are both deswollen and their contrasts are too similar. The HSS nanocapsules vitrified at 20 °C (Figure 4B) show a light-gray area at their centers surrounded by a darker shell. This proves a successful core removal and the presence of cavities. However, the polymeric shells are again indistinguishable. The HSS microgels show mismatched radii compared to DLS analysis. This is, on one hand, due to the high concentration of the microgels in the Cryo-TEM image: Neutral microgels deswell with increasing concentration;9,60 on the other hand, the freezing can lead to deformation of the soft microgels in the ice layer. In combination with energy-filtered TEM (see Figure S.9), the Cryo-TEM verifies a successful core removal. However, no reliable information on size, cavity or shell composition can be gained. To unravel information on the 3D structure via TEM, compartmentized staining in combination with powerful analysis methods are required.61 Yet, the method of choice is small-angle neutron scattering. It reveals understanding of the interplay between the two shells and precisely characterizes the structure of the microgels in presence and absence of the silica core. pNIPAM and pNIPMAM show both different neutron scattering length densities (ρpNIPAM = 0.814 × 10−6 Å−2 and ρpNIPMAM = 0.698 × 10−6 Å−2) and polymer densities due to the cross-linker concentrations employed during the shell polymerizations. Contrast matching is an elegant way to reveal information on the radial distribution of the shells. Three distinct temperatures where investigate and compared to the simulated counterparts to fully understand the swelling. They correspond to the various swelling states of the double-shell microgels: the complete deswollen state at 50 °C and the swollen state at 20 °C, and 40 °C the intermediate state (good solvent for the inner shell and bad solvent for the outer shell). The relative polymer volume fraction of the single-shell microgels obtained from the fits of experimental scattered intensities with an appropriate form factor model are discussed and compared to the corresponding computer simulations in the Supporting Information (see Figure S.10). Briefly, the CS microgels show the typical behavior of a stiff core surrounded by a soft polymeric shell. Above the VPTT, the shell presents a high polymer density without fuzzy periphery. In contrast, below the VPTT, the radial profile illustrates a larger radius with a decrease in polymer density and a decaying volume fraction toward the surface of the microgel. The radial profiles of the corresponding HS gels reveal a cavity F


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Figure 5. Scattering curves of the (A) CSS and (B) HSS microgels probed at 50 °C (red circles), 40 °C (green triangles), and 20 °C (blue squares) with corresponding form factor fits (continuous lines). For clarity, all scattered intensities probed at 40 °C were multiplied by a factor of 10 and at 50 °C by 100. Relative radial density profile of the (C) CSS microgels and (D) HSS nanocapsules obtained from form factor analysis at 50 °C (red solid lines), 40 °C (green dashed-dotted lines) and 20 °C (blue dashed lines). The contrast matched silica core is represented by the gray box. Relative radial density profiles obtained from MD simulations of (E) CSS and (F) HSS microgels when the solvent is bad for both shells (red solid lines), good for the inner and bad for the outer shell (green dashed-dotted lines), and good for both shells (blue dashed lines). The core is shown in gray.

5F, respectively. The most apparent difference in the radial profiles of CSS and HSS microgels is the arising cavity. At full collapse (red lines), the cavity is conserved and the profiles resemble to box-like profiles. The internal structure of the HSS is comparable to the CSS with a slight decrease of the overall polymer density related to the loss of restrain. In addition, SANS unravels a cavity larger than the sacrificial silica core. These effects are not accounted in the simulations. The homogeneous cross-linking distribution in the networks results in a distinct swelling behavior compared to the real microgels with inhomogeneous cross-linking density. Because of the faster reaction rate of the cross-linker compared to the monomers,

due to higher cross-linking density compared to the outer pNIPAM shell. As consequence, the radial profile at 20 °C shows a higher volume fraction of the inner shell. Similar behavior has been observed for the pNIPMAM core pNIPAM shell microgels. The polymeric density of the swelling core increases as response on a surrounding deswollen shell.21 However, here, the presence of the incompressible core increases this effect, as the inner network cannot expand toward the center. In addition, our system offers the possibility to investigate the hollow analogues. The radial density profiles of the HSS nanocapsules obtained from SANS and from simulation are shown in Figures 5D and G


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predicted by computer simulation and studied by means of small-angle neutron scattering. The double-shell microgels with incompressible silica core reveal unique behavior: A significant interpenetration of the two networks at temperature between the distinct VPTTs is observed. The swelling of the inner pNIPMAM shell leads to an increase of the relative polymer volume fraction of the outer pNIPAM shell when compared to the fully deswollen state. This unpredicted interpenetration of a softer shell into a rigid one might be significant regarding further studies of the behavior in highly crowded environments. After core removal, the shell interpenetration vanishes and a push−pull effect occurs: Swelling of the inner pNIPMAM shell into the cavity of the microgel is detected when the outer network remains deswollen. Complete swelling then leads to a pulling of the inner by the outer shell resulting in an increase of the void size. The cavity is preserved independently of the swelling or deswelling of the distinct shells. These findings are in good agreement with our computer simulations, which predicted that a highly cross-linked inner shell is required to generate hollow microgels at all swelling degrees. We showed that MD computer simulations are a good method to predict the main features of microgels. However, due to the simplifications of the structure of the polymer networks as well as the interactions, the model cannot completely describe the real swelling/deswelling processes. Therefore, powerful methods as SANS are indispensable to reveal the internal structure of such complex microgel structures. Comparing the presented microgels to the system with inverse shell composition, namely an inner pNIPAM and an outer pNIPMAM shell,34 both systems show that in the fully deswollen and fully swollen state the shells are only slightly distinguishable. However, at the intermediate swelling state the internal microgel structures disclose pronounced differences. The microgels with a collapsed inner and a swollen outer shell show similar density profiles with and without silica core, with a slight increase of the cavity size.34 In contrast, our system with a swollen inner and a collapsed outer shell shows a considerably stronger interplay of the two networks, resulting in shell interpenetration in the presence of the rigid core and a decrease of the void size in its absence. We showed that independently of the collapse of the outer shell, the cavity and the structural integrity of the nanocapsules are preserved. The study on the mutual effect of the two networks in combination with previous observations21,34,61,67 enables a broad toolbox to rigorously modify the chemical and physical properties of microgels. This is of great interest regarding the diverse functionality and application as delivery systems. The employment of hollow microgels for controlled uptake and storage in the cavity followed by a regulated release is very promising.33,34 Further studies to elucidate how the incorporation of different guest species in the cavity affects the thermoresponsiveness and the structure of the nanocapsules are in progress.

the cross-linking density decreases toward the outer periphery of the microgels.45,64 These findings indicate that more effort must be done in modeling the network for the simulations to have a more accurate description of the swelling behavior. At intermediate swelling (green dashed-dotted lines), the solvent is good for the inner but bad for the outer shell. This explains the decrease of the volume fraction of the pNIPMAM shell observed in both profiles. The shells expand toward the inner and outer periphery. Especially in SANS, the radial profile differs considerably from the distribution of the polymer fraction in the corresponding CSS microgels. The interpenetration of the shells cannot be observed for the hollow spheres. This relates to the ability of the pNIPMAM shell to swell into the solvent-filled cavity when expanding. This effect causes then a decrease of the size of the void. However, as predicted by computer simulations, the highly cross-linked inner network is only partially filling the cavity. At full swelling (blue dashed lines), the distributions of the polymeric densities obtained by SANS are again comparable to the CSS microgels. The solvent is good for both shells and the polymer networks expand to their maximum. As discussed above, the profiles resulting from simulations differ from the SANS profiles due to the simplified architecture of the network. Finally, the swelling of the HSS microgels from the fully collapsed to the fully swollen state can be described by a push− pull effect: Below the VPTT of pNIPMAM, the deswollen outer network pushes the swollen inner shell toward the center, leading to a decrease of the cavity size. When the temperature is decreased further (below the VPTT of pNIPAM), the outer shell swells and pulls the inner network toward the outer periphery, resulting in an increase of the cavity size. Core−shell and core−double-shell systems with inverse shell composition, meaning an inner pNIPAM and an outer pNIPMAM network have been studied previously.34,41,65,66 Schmid et al. investigated a similar system with inverse shell composition, meaning the swelling of a polymeric network in the constraints of a swollen shell and the stiff core or cavity.34 The internal structure of their system is very similar to ours above and below the VPTTs of the polymers. The most important difference consists of the intermediate swelling state: In their study the outer shell swells, while the inner network is deswollen; our microgels have opposite behavior. The internal structures of both systems are distinctly different as the outer constraint of the inner network is different. In their study, upon cooling, the outer network swells first which does not hinder the expansion of the inner shell on the one hand. On the other hand, it does not lead to a decrease of the cavity size compared to the fully deswollen state in the hollow system. Finally, the experimental findings reveal detailed information on the real structural behavior of double-shell microgels which were not predicted by our simplified computer simulation model: (i) an apparent interpenetration of an expanded inner shell into the deswollen outer network is spotted in the presence of an incompressible core; (ii) the inner shell undergoes a push−pull effect related to the swelling/deswelling of the outer shell and is able to maintain a solvent-filled cavity at all swelling states.

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ASSOCIATED CONTENT

* Supporting Information S

CONCLUSIONS We investigated the interplay between two polymeric shells with distinct VPTTs in doubly thermoresponsive microgels with either a rigid silica core or the corresponding cavity in the center. The internal structure of the microgels has been

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b02722. Additional supporting research data for this article may be accessed at no charge at https://hdl.handle.net/ 21.11102/bf9a64b7-10ca-11e8-80f7-e41f1366df48. H


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Additional computer simulation results; characterization of silica nanoparticles as well as core−shell (CS) and hollow shell (HS) microgels (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (W.R.). ORCID

Monia Brugnoni: 0000-0003-2220-3645 Andrea Scotti: 0000-0002-8988-330X Andrij Pich: 0000-0003-1825-7798 Igor I. Potemkin: 0000-0002-6687-7732 Walter Richtering: 0000-0003-4592-8171 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Dr. Otto Virtanen for providing homopolymeric pNIPAM microgels and Dr. Khosrow Rahimi for the help with the Cryo-TEM imaging. Financial support from the SFB 985 “Functional Microgels and Microgel Systems” of Deutsche Forschungsgemeinschaft within Project A3 and from the International Helmholtz Research School of Biophysics and Soft Matter (IHRS BioSoft) is greatly acknowledged. Dr. Andrea Scotti acknowledges the support through an Alexandervon-Humboldt scholarship. The work was supported by the Government of the Russian Federation within Act 211, Contract # 02.A03.21.0011, and the Russian Foundation for Basic Research. The authors gratefully acknowledge the computing time granted by the John von Neumann Institute for Computing (NIC) and provided on the supercomputer JURECA10 at the Jülich Supercomputing Centre (JSC). This work is based upon experiments performed at the KWS-2 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany.

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ADDITIONAL NOTE Please note that there is a typographical error in the equations in the original paper.21 a

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Swelling of a Responsive Network within Different Constraints in Multi

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