Cellulose Nanocrystal Microcapsules as Tunable Cages for Nano

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN

Article

Cellulose Nanocrystal Microcapsules as Tunable Cages for Nano- and Microparticles Chunhong Ye, Sidney T. Malak, Kesong Hu, Weibing Wu, and Vladimir V. Tsukruk ACS Nano, Just Accepted Manuscript • DOI: 10.1021/acsnano.5b03905 • Publication Date (Web): 04 Oct 2015 Downloaded from http://pubs.acs.org on October 6, 2015

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

ACS Nano is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

1

9/25/2015

Cellulose Nanocrystal Microcapsules as Tunable Cages for Nano- and Microparticles Chunhong Ye†, Sidney T. Malak†, Kesong Hu†, Weibin Wu‡, Vladimir V. Tsukruk†,* †

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332 (USA)

‡

School of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, P. R. China

Abstract: We demonstrate the fabrication of highly open spherical cages with large and through pores using high aspect ratio cellulose nanocrystals with “haystack” shell morphology. In contrast to the traditional ultrathin shell polymer microcapsules with random porous morphology and pore sizes below 10 nm with limited molecular permeability of individual macromolecules, the resilient cage-like microcapsules show a remarkable open network morphology that facilitates across-shell transport of large solid particles with a diameter from 30 nm to 100 nm. Moreover, the transport properties of solid nanoparticles through these shells can be pH-triggered without disassembly of these shells. Such behavior allows for the controlled loading and unloading of solid nanoparticles with much larger dimensions than molecular objects reported for the conventional polymeric microcapsules.

Keywords: caged microcapsule, cellulose nanocrystals, particle transport, particle loading *

* Corresponding author. E-mail:[email protected]

ACS Paragon Plus Environment

ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

2

TOC:


Page 2 of 22 9/25/2015

Page 3 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

3

9/25/2015

Recent developments in the drug delivery, biomedical field, the food industry, and the area of biology applications have made clear there is a need for an efficient encapsulation and the robust delivery systems with the capability to accurately target and release various active ingredients such as drugs, flavors, proteins, or even living cells. 1 , 2 , 3 , 4 Intensive research activities are focused on the fabrication of various structures including polymer composites,5 microcapsules,6 microchambers,7 microwells8 and gripers. 9 These structural designs received extensive attention for controlling transport and permeability in response to specific stimuli such as pH,10 temperature,11 or ionic strength12 by employing a variety of polyelectrolytes, biopolymers, nanoparticles, or flakes.13,14,15

Versatile microcapsules for delivery systems should exhibit selective encapsulation of various cargos with controllable permeability for modulated loading/unloading behavior, while also possessing robust mechanical properties to protect entrapped materials from varying loads. 16 One of the more popular designs is the thin shell microcapsule fabricated with Layer-by-Layer (LbL) assembly. 17, 18 ,19 , 20 However, in biological and biomedical fields like drug delivery, cell encapsulation, and tissue engineering, biocompatibility and biodegradability are primary considerations, which is a main issue for delivery systems based on current microcapsules due to the cytotoxicity of synthetic cationic components. 21

Furthermore, currently explored microcapsules which are

mostly composed of synthetic polymers or biopolymers usually possess dense shells with a mesh size of few nanometers for ionic-bonded shells and usually below 10 nm for hydrogen-bonded shells.10,22,23,24,25,26,27,28 These uniform shells are only permeable to small molecules or mid-sized macromolecules (well below 106 Daltons) even in a highly swollen state.29,30 Thus, across-shell transport and encapsulation of large objects such as nano- and microparticles is forbidden with current material choices.

Thus, new

designs of stable microcapsules capable of controlling transport of nano- and microparticles should be thought.

In order to assemble a novel type of microcapsules, which can load and unload large solid particles and remains stable, we turned to anisotropic particulate materials


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

Page 4 of 22

4

9/25/2015

components such as one-dimensional (1D) cellulose nanocrystals (CNCs).

These

materials are widely-available, inexpensive and biocompatible, and can be prepared in large quantity by acid hydrolysis of cellulose materials.31,32 CNCs have high elastic modulus, low thermal expansion, non-toxicity and high surface area, and inherently renewable.32, 33 , 34 CNCs have been utilized as a reinforcing component in polymer nanocomposites with outstanding mechanical properties 35,36 but were rarely exploited for design of microcapsules.37

Herein, we utilize the chemically functionalized cellulose nanocrystals to fabricate open “haystack” shell microcapsules capable of unique across-shell transport of large solid nanoparticles (up to 100 nm) by using conventional LbL assembly (Figure 1).

Figure 1. Preparation of “cellulose-on-cellulose” microcapsules via LbL assembly and their encapsulation/release behavior under different pH conditions.

In striking contrast to conventional polymer LbL microcapsules with limited molecularlevel permeability, these cage-like microcapsules possess large open and through pores with remarkable stability in extreme acidic and basic conditions.

And the

remarkable elastic modulus of CNCs up to 180 GPa also suggests potential for high stability of the cellulose nanocrystal based capsules.

Furthermore, these purely

cellulose microcapsules demonstrate pH-triggered encapsulation and release of relatively

large

particles

(up

to

100

nm),

demonstrating


the

capability

of

Page 5 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

5

9/25/2015

loading/unloading of a variety of solid species unavailable in current polymer microcapsules, such as sensors for acidic leakage and neutralizing by release entrapped components.

RESULTS AND DISCUSSION The cellulose nanocrystals utilized here were obtained by hydrolyzing softwood kraft pulp with sulfuric acid (64% w/w) according to previously publication,31 which show a negative charge of -38 ± 1.6 mV due to the presence of the sulfonic acid ester groups on the surface. For further verifying the chemical structure, we collected ATR-FTIR spectra of CNCs by deposition on silica crystal (Figure 2). A representative spectra of cellulose was obtained with a characteristic peak from C-O bond of cellulose glucose ring was also observed at 1031 cm-1. 38 The weak peaks around 1244 and 1330 cm-1 were attributed to the small amount of sulfonic acid ester group introduced by acid hydrolysis.39 The broad peaks centered at 3338 and 2901 cm-1, which corresponds to the –OH and C-H stretching vibrations, respectively. 40

The peak at 1646 cm-1

originated from the H2O vapor from atmosphere absorbed onto CNC surfaces. The CNC possess a high aspect ratio, rod-like morphology with a length of around 150 nm and an average diameter of 6.5 ± 1.2 nm (an aspect ratio of more than 20) (Figure 2a). The LbL assembly was carried out at a mild pH condition (pH 5.5) to minimize structural changes of the capsules and maximize the surface charge for enhanced stability. After the deposition of CNCs on the templates, a thermal treatment (85°C for 10 min) was carried out to promote the formation of hydrogen bonding network. 41 Furthermore, a PEI pre-layer to ensure the LbL assembly by recharging the negative surface charge of the silica templates, facilitating the absorption of the first CNCs layer onto the templates (Figure 1). Control experiment without a PEI pre-layer and the thermal treatment showed incomplete assembly without formation of shells. The FTIR spectrum for CNC microcapsules is shown in Figure 2c. It has a broad peak at 3340 cm-1 associated with stretching vibration of –OH group, which is shifted to lower frequency as compare to expected position around 3500 cm-1 and a noticeable shoulder peak

at 3290 cm-1.

Such features can be ascribed to the formation of


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

6

Page 6 of 22 9/25/2015

hydrogen bonding, altering the strength of –OH mode as discussed in previous reports. 42 , 43 In fact, hydrogen bonding was also introduced between the individual CNCs after drop-casting,

44

thus indicating hydrogen-bonded network in these

components. Characteristic peak of PEI pre-layer was not detected because of its trace amount.

Figure 2. (a) AFM image shows the “haystack” morphology with densely packed individual cellulose nanocrystals; (b, c) ATR-FTIR spectra of individual cellulose nanocrystals (b) and PEI-(CNC)15 microcapsules (c) deposited by drop-casting; (d) Variation in the zetapotential for PEI-(CNC)n shells on silica templates; (e, f) Shell thickness and microroughness of cellulose nanocrystal shells with different numbers of layers.

AFM imaging of CNC layers demonstrated formation of dense, random packing of cellulose nanocrystals with characteristic “haystack” morphology (Figure 2a).35 In order to confirm the sustainable growth of the multilayer shells on silica spheres, the zetapotential of the templates was monitored after each deposition step and the shell thickness was measured from AFM images (Figure 2d, e).

We found that the original silica spheres have a high negative charge (-67 ± 0.5 mV). After deposition of the cationic PEI pre-layer, the zeta-potential increased to +56 ± 2.6


Page 7 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

7

9/25/2015

mV which reflects surface recharging by cationic polymer coating (Figure 2d).

A

subsequent deposition of one layer of negatively charged cellulose nanocrystals caused the zeta-potential to switch back to a negative charge (-35 ± 0.3 mV), which indicates a traditional charge-overcompensated mechanism of LbL growth.17

This variation

demonstrated that the deposition of the first CNC layer is driven by conventional ionic pairing.

Further buildup of CNC layers does not shift the surface potential from a

negative zone suggesting the hydrogen bonding of similarly charged nanocrystals as a major driving force for shells growth as suggested from IR studies.41,45 A slight increase of the surface charging for thicker shells (to around -40 mV) might be related to partial accumulation of counter-ions during long adsorption processes.

Figure 3. General morphology of cellulose nanocrystals microcapsules. (a, b) Large scale AFM topography images of dried PEI-(CNC)6 microcapsules after core dissolution (z-scale: 100 nm); (c) High resolution 3D AFM height image with wrinkles (z-scale: 60 nm), corresponding phase image (d) (z-scale: 80°); (e, f) CLSM image of microcapsules in aqueous solution and 3D confocal image of the shell labeled with fluorescent isothiocyanate (FITC).


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

8

Page 8 of 22 9/25/2015

Next, direct measurement of the thickness of PEI-(CNC)n shells with different layers by atomic force microscopy (AFM) confirmed consistent, near-linear increase in their thickness (Figure 2e). AFM measurements were conducted on dry shells after removal of silica templates (Figure 3a,b).66 The shell indicted a gradual increase in thickness, from 6.0 ± 0.5 nm for n = 3 to 17.0 ± 2.0 nm for n = 18.

Unlike conventional polymer microcapsules composed of traditional polyelectrolytes with an average increment of 2-4 nm per bilayer (depending upon molecular weight),46,47, 48 the CNC shells exhibited a lower growth increment (average increment around 1 nm per layer). Such low growth rate in comparison to the diameter of CNC indicates an “incomplete” layer formation with a highly open porous morphology, which is only partially filled at a single deposition cycle due, probably, to strong repulsive interactions of similarly negatively-charged cellulose nanocrystals.

Indeed, the

characteristic “haystack” morphology of randomly packed 1D rigid high-aspect ratio nanocrystals is observed from the AFM images of microcapsule shells (Figure 3). And the AFM scans for microcapsules with different layers clearly revealed that the shell morphology changed from highly porosity to much more denseness as the assembled layer increased from 3-layer to 18-layer (Figure 4).

This random packing resulted in higher microroughness of CNC shells of 4.8 ± 0.6 nm (in selected areas of 1×1 µm with z-resolution of 0.17 nm) (Figure 2f). The roughness almost kept the same, only slightly increased when the assembled layer reached 18, due to the grainy morphology as demonstrated by high resolution AFM image (Figure 4f). Gradually, the dense “haystack” morphology of cellulose nanocrystals is formed for thicker shells with signs of local aggregation and bundling of nanocrystals (Figures 4). Less wrinkles of the dried hollow shells formed with an increasing number of CNCs layers from 3 to 18 layers, attributed to the higher rigidity of CNCs shells with the increased thickness (Figure 4a, c, e).


Page 9 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

9

9/25/2015

Figure 4. Varied morphologies of “CNC-on-CNC” microcapsule with different layers of cellulose nanocrystals revealed by AFM images. (a, b) 3, (c, d) 9, (e, f) 18 layers of cellulose nanocrystals. Z-scale (a, c): 100nm, (e): 200 nm, (b, d): 50nm and (f): 110 nm.

High-resolution AFM images revealed an aggregated texture from closely packed cellulose nanocrystals and their bundles for thicker shells, indicating a somewhat reduced porosity of the shells (Figure 4b, d, f). The phase images further confirmed packed but clearly visible individual nanocrystals within these bundles and “haystack” morphology (Figure S1). And all the microcapsules have a diameter of 3.8±0.5 µm as defined by the original template size.49,50,51

Indeed, this highly porous morphology of CNC shells is confirmed by TEM analysis (Figure 5). The high resolution TEM images not only indicated CNC capsules with random assembled high-aspect ratio “haystack” nanocrystals, but also clearly revealed


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

10

Page 10 of 22 9/25/2015

extremely mesh texture of the shell with large open, nearly-rounded through nanopores (Figure 5a, b). Such morphology is distinct for traditional LbL polymer shells with random fractal network of pores. The mesh size was significant reduced by increasing the shell layers (Figure S2). Quantitative analysis of the TEM images for thickest shells (PEI-(CNC)18) showed a large pore size of 34 ± 3.8 nm, which is in an agreement with the pore size estimated by the nanoparticle permeability measurement as discussed above. These microcapsules are completely “open” to the FITC-labeled dextran with maximum available molecular weight (2 MDa), indicating large size of open pores above 30 nm.

Figure 5. (a) TEM image of PEI-(CNC)18 microcapsules after core dissolution; (b) High resolution TEM image taken at the flat area of CNC shell with 18 layers; (c-d) TEM micrographs taken the edge of PEI-(CNC)12 microcapsules evidencing the encapsulation of 50 nm PS beads at pH 5.5 (c) and the releasing after adjusting pH back to 1.5 (d).


Page 11 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

11

9/25/2015

Moreover, as we observed the thinnest PEI-(CNC)3 shells are permeable to large PS particles with a diameter of 100 nm (fluorescence-labeled polystyrene (PS) latex particles) confirming a highly porous nature of the CNC shells and suggesting a mesh size of more than 100 nm (Figure 6a). In contrast, the “open” network became partially “closed” for a 12-layer shell, in which, the 50 nm PS particles were unable to penetrate into the interior (Figure 6b).

Figure 6. Confocal microscopy images of PEI-(CNC)n microcapsules exposed to fluorescence labeled PS latexes in phosphate solution at pH 5.5: (a) PEI-(CNC)3 exposed to Rhodamine labeled-PS latex beads with a diameter of 100 nm (particles penetrate shells); (b) PEI-(CNC)12 microcapsules exposed to FITC labeled-PS latex beads with a diameter of 50 nm (particles do not penetrate shells), (capsules in the right side are out of CLSM focus section).

Table 1 summarizes the permeability of the PS particles through the CNC shells with varied thickness in phosphate solution at pH 5.5. Increasing the shell thickness resulted in a gradual decrease of cut-off PS particle size down to 30 nm for a 12 layer shell, which reveals a gradual densification of the shells and porosity reduction.10,22 The observation is consist with the morphology change as demonstrated by AFM and TEM measurements (Figure 4, 5a, b and S2). And this correlation allows to control the across-shell transport of solid particles with different diameters. The CNC shells with 12 layers are permeable only for the smallest particles with a diameter of 30 nm, indicating the threshold of the shell porosity within 30-50 nm (Table 1). It is worth noting that the surface functionality of PS beads does not define the across-shell


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

Page 12 of 22

12

9/25/2015

transport thus indicating that Coulombic interactions play minor role in the particle transport in these open pore morphologies in contrast to traditional polymer microcapsules. Table 1. Permeability of PEI-(CNC)n microcapsules with different number of layers to fluorescence labeled PS particles with different diameters and surface functionalization. Particle size layers

PS latex particle diameter, nm (charges are indicated) A-100 nm (+)

S-100 nm (-)

Bare-50 nm (0)

C-30 nm (-)

3-layers 6-layers

+ ⁻

+ ±

+ +

+ +

9-layers 12-layers

-

-

± –

+ +

Symbols “+”, “–” and “±” indicate permeable, impermeable and partially permeable microcapsules, respectively; PS latexes: A-100: amine-modified, a diameter of 100 nm; S-100: sulfate-modified, a diameter of 100 nm; Bare-50: Non-modified, a diameter of 50 nm; C-30: carboxylate-modified, a diameter of 30 nm.

Thus, all experimental results indicate that CNC shells possess highly open morphology with large through pores in strike contrast to conventional polymer microcapsules with random pore network that are permeable to macromolecules with a hydrodynamic diameter below 10 nm.10, 52

Such a significant difference can be

attributed to the very peculiar “haystack” morphology of shells from high aspect ratio cellulose nanocrystals.

Unlike the randomly packed and highly overlapped flexible

coiled macromolecular chains, rigid high aspect ratio nanocrystals are difficult to bend. Random packing of these nanocrystals leaves widely open space serving as large pores.

Thus, instead of forming a compliant dense mat with low free volume by

overlapped flexible chains, the CNC shells possess “haystack” morphology with large through openings between bundles and nanocrystals of cellulose nanocrystal shells.

Finally, the encapsulation and release property of these cage-like microcapsules can be controlled by external pH (Figure 7).

Controlled release work for 50 and 100 nm

particles and is not efficient for 30 nm particles, probably, because of large size of open pores. For instance, PS beads with a diameter of 50 nm were unable to permeate the PEI-(CNC)12 shells at pH 5.5 (Figure 7a). But when the microcapsules were exposed to


Page 13 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

13

9/25/2015

the same particles at very low acidic pH 1.5, the shells became “open” and allow penetration of these large particles (Figure 7b). This change in transport properties was also confirmed by high resolution SEM images which show a high density of PS particles on non-permeable shells, but only few particles on the surface of permeable shells at pH 1.5 (Figure 7a, b insert images).

Figure 7. Confocal microscopy images showing the permeability of PEI-(CNC)12 capsules to PS beads with a diameter of 50 nm at different pH. (a) PEI-(CNC)12 capsules exposed to 50 nm-PS beads at pH 5.5; (b) PEI-(CNC)12 capsules exposed to 50 nm-PS beads at pH 1.5; (c) Capsules in “b” adjusted to pH 7.5; (d) Capsules in “c” adjusted to pH 1.5. Inserts (a, b) are high resolution SEM images at corresponding conditions. Inserts (c, d) are the fluorescent intensity profiles across the capsules (indicated by white lines) show different fluorescent intensity inside capsules in permeable and non-permeable states.

Furthermore, the PS particles into the interior of the capsules can be encapsulated by changing the pH of the solution from 1.5 to 7.5, showing much stronger photoluminescence intensity inside of the capsules as compare to that of exterior (Figure 7c and insert). Finally, the encapsulated particles can be completely released in several minutes by adjusting the solution pH from 7.5 back to 1.5, which the interior and


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

Page 14 of 22

14

9/25/2015

exterior of capsules have the same fluorescence intensity (Figure 7d, insert). It is worth to mention that the shells show bright fluorescence signal, suggesting the additional absorbance of PS nanoparticle onto the shell during transport.

The encapsulation and release were also revealed by TEM images (Figure 5c,d). As was observed, for the encapsulated situation, PS particles only present in the collapsed microcapsule regions, without any noticeable particles seeing in the background surrounding microcapsules (Figure 5c). In striking contrast, as the pH adjusted back to acidic conditions and the PS particles are released through the CNC shells, both the capsules and background are populated with the nanoparticles (Figures 5d and S3).

We suggest that the pH-controlled loading/unloading behavior can be attributed to the protonation of oxygen in the ether groups and sulfonic acid ester on cellulose in acidic condition similarly to those reported for traditional polymer microcapsules.21, 53 , 54 Changing in external pH results in dramatic changes in surface charges of cellulose nanocrystals which are rich in carboxylic and hydroxylic surface groups as well as supporting PEI prime layer riched in amino groups.

As known from z-potential

measurements, CNC loses strong negative charge and PEI keeps high positive charge at low pH, but at intermediate pH CNC becomes highly negatively charged while PEI remains positively charged.55 Finally, at pH above 7.5 both shells component become negatively charged.

Changing in electrostatic interactions might affect hydrogen

bonding network of the cellulose nanocrystals expanding it at strongly repulsive conditions (low pH). On the other hand, intermediate pH where repulsive Coulombic interactions are absent and van der Waals interactions stabilizes dense haystack morphology due to stronger and denser hydrogen bonding network. Such “compacted” shell morphology prevents the particle transport around neutral pH but permits particle transport through loosely packed haystacks at extremely acidic condition. It is important to note that the CNC microcapsules remain stable under extreme acidic condition in striking contrast to conventional polymer LbL shells which readily dissolve at extreme pHs or require crosslinking to facilitate the reversible shape changes.56,57 The stability of the CNC microcapsules can be attributed to wet-strength between the individual


Page 15 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

15

9/25/2015

cellulose nanocrystals which is introduced by the additional thermal treatment that replaces traditional crosslinking.58,59,60

CONCLUSIONS In conclusion, we demonstrated the fabrication of single component robust cage-like microcapsules from cellulose nanocrystals with highly open “haystack” shell morphology capable of loading and unloading large solid particles with a diameter up to 100 nm in contrast to traditional polymer LbL microcapsules with minute permeability of smaller molecules.

These cellulose nanocrystal microcapsules with controlled across-shell

transport and high open porosity present a novel candidate for prospective functional materials relevant to prospective applications in bioengineering for controlled encapsulation of solid nanoparticles with nanoscale and sub-micron dimensions.

EXPERIMENTAL SECTION Materials. Cellulose nanocrystals (CNCs) were obtained using a previously published method.31 Briefly, softwood kraft pulp without any treatment was ground in a Wiley Mini-Mill to pass through a 20-mesh screen.

Following this, 50.0 g of milled pulp

powder was hydrolyzed by treating with 500 ml H2SO4 (64% w/w) for 45 min at 45°C. Then, the hydrolysis was halted by diluting the solution 10 times with Nanopure water (18.2 MΩ cm; Synergy UV-R, EMD Millipore). The solution was centrifuged at 5000 rpm at 4°C for 10 min to collect the hydrolyzed pulp, followed by dialysis with regenerated cellulose dialysis tubing (12,000~14,000 MWCO, Thermal Scientific) against Nanopure water until the pH reached a constant value.

Sonication was

performed on the cellulose nanocrystal aqueous using a Branson Sonifier for 30 min with in an ice bath. The resulting colloidal suspension was centrifuged at 5000 rpm at 4°C for 5 min, and then the cloudy supernatant was collected and stored at 4 °C prior to use.

Silica spheres with a diameter of 4.0±0.2 µm as 10% dispersions in water were obtained from Polysciences, Inc.

Sodium phosphate dibasic, sodium phosphate

monobasic, sulfuric acid and hydrofluoric acid (HF 48-51%) were purchased from BDH.


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

Page 16 of 22

16

9/25/2015

Ammonium fluoride (AF) was obtained from Alfa Aesar. Branched polyethylenimine (PEI) with Mn = 10,000, fluorescent isothiocyanate (FITC) and fluorescence–labeled polystyrene latex particles with sulfate/carboxylate/amine modified surface at various diameter were obtained from Sigma-Aldrich. Fluorescence-labeled polystyrene latex particles with a diameter of 50 nm were purchased from Magsphere Inc.

All the

materials were used without further purification. Single-side polished silicon wafers of the {100} orientation (University Wafer Co) were cut to a typical size of 10 mm × 20 mm and cleaned in piranha solution as described elsewhere.61

Fabrication of “PEI-(CNC)n” Capsules. Silica spheres were dispersed in 0.5 mg/ml PEI solution (prepared in 0.1M NaCl, pH 7) to make a prime layer to stabilize the LbL process. After coating in PEI the silica spheres were dispersed in 1 mg/ml cellulose nanocrystals aqueous for deposition with slow rotation to avoid the formation of air bubbles for 15 min, followed by 2 washing cycles with 50% and 100% methanol by centrifugation at 2,000 rpm for 2 min to remove the excess CNC. Then, the samples underwent a thermal treatment in a vacuum oven at 85°C for 10 min.

Multilayer

capsules were obtained by repeating the procedure described above with overall fabrication taking more than 12 hours for thickest shells explored (n=18). To dissolve the silica cores, the capsules with the cores were exposed to 1M HF/4M NH4F solution (pH≈5.5) overnight, followed by dialysis with slide-A-lyzer dialysis cassettes (100,000 MWCO, Thermal Scientific) against Nanopure water at pH 5.5 for 72 hours with repeated changes of water (Figure 1).62,63

Zeta-Potential Measurements. The surface potential of the silica spheres after every deposited layer was measured in aqueous solutions (with typical concentration of around 0.1 % w/w) using a Zetasizer Nano-ZS (Malvern).

Potential values were

obtained at ambient conditions by averaging three independent measurements of 30 runs each.

Microscopies.

Surface topography of the hollow capsules and the cellulose

nanocrystals in dry state was examined using AFM.64 The height and phase images


Page 17 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

17

9/25/2015

were collected from a Dimension-3000 (Digital Instruments) in tapping mode using silicon V-shape cantilevers with a spring constant of 46 N/m. The capsule’s single wall thickness was determined by taking half the height of the collapsed flat regions on dried capsules using bearing analysis from the NanoScope software to generate height histograms. 65 , 66 The microroughness was measured in smooth regions of the microcapsule from selected 1 µm×1 µm areas without wrinkles.65

SEM micrographs were collected using a Hitachi SU8010 cold field emission SEM with an ultraclean vacuum system (turbo pump and an oil-free dry-scroll pump) and a secondary electron detector (1.0 nm resolution) at an operating voltage of 2-5 kV. To reduce charging, Au was sputtered on samples using a Denton Vacuum IV at 50 mTorr.

TEM imaging was conducted on a Hitachi HT7700 by drop-cast the sample onto a carbon-formvar TEM grid (TED PELLA, INC). To minimize radiation damage and use the smallest objective aperture for enhancing contrast, measurements were operated at 80 kV acceleration voltage.

Confocal images of capsules were obtained with a LSM 510 Vis confocal microscope equipped with a 63×1.4 oil immersion objective lens (Zeiss). Capsules were visualized by adding FITC solution (1mg/ml in phosphate buffer at pH 5.5) to the capsule suspension in Lab-Tek chambers (Electron Microscopy Science). Excitation/emission wavelengths were 488/515nm. To investigate the permeability of the capsules, 200 µl hollow PEI-(CNC)12 capsule suspensions were added to several Lab-Tek chambers, which were then mixed with 30 µl of 2.5% (w/v) fluorescence-labeled polystyrene latex particles with different surface functional groups and various diameters. These mixtures were allowed to settle for several hours to make sure the movement of latex particles in the solution reached equilibrium.


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

Page 18 of 22

18

9/25/2015

For examining pH-triggered encapsulation and release, 200 µl PEI-(CNC)12 hollow capsule suspensions mixed with the PS latex particles with a diameter of 50 nm at pH 5.5 was added to a Lab-Tek chamber. After taking CLSM images, the chamber was 3/4 filled with phosphate buffer at pH 1.5. The liquid in the chamber was then sucked out to check the permeability at this condition. Following this, the chamber was refilled with another phosphate buffer at pH 7.5 to check the encapsulation. Finally, the liquid in the chamber was replaced with phosphate buffer at pH 1.5 again to check the release.

ATR-FTIR

measurements.

ATR-FTIR

measurements

of

individual

cellulose

nanocrystals and CNC microcapsules were carried out on a Bruker FTIR spectrometer Vertex 70 equipped with a narrow-band mercury cadmium telluride detector according to the procedure described previously.67 Sample was deposited onto silica crystal by drop-cast from aqueous suspension and air dried. The spectra were collected in the range of 4000-900 cm-1 with a resolution 1 cm-1 and accumulation of 100 scans.

Acknowledgement The work was supported by the National Science Foundation CBET-1402712 and Air Force Office for Scientific Research, FA9550-14-1-0015 Awards.

Supporting Information Individual nanocrystals within the shell of cellulose nanocrystal microcapsules demonstrated by high resolution AFM phase images with different layers (Figure S1). Highly porous morphology of hollow microcapsules with different layers revealed by TEM images (Figure S2). Comparison of the encapsulation and release of PS nanoparticleS by adjusting the pHs revealing by large scale TEM images (Figure S3). The Supporting Information is available free of charge on the ACS Publications website at DOI: nn-2015-039059.


Page 19 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

19

9/25/2015

REFERENCES [ 1 ] Ariga, K.; Ji, Q.; Hill, J. P.; Bando, Y.; Aono, M. Forming Nanomaterials as Layered Functional Structures toward Materials Nanoarchitectonics. NPG Asia Materials 2012, 4, e17. [2] Stuart, M. A.; Huck, W. T.; Genezer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, L.; Tsukruk, V. V.; Urban, M.; et al. Emerging Applications of Stimuli-Responsive Polymer Materials. Nature Materials 2010, 9, 101-113. [3] Sukhorukov, G. B.; Rogach, A. L.; Garstka, M.; Springer, S.; Parak, W. J.; Munoz-Javier, A.; Kreft, O.; Skirtach, A. G.; Susha, A. S.; Ramaye, Y.; et al. Multifunctionalized Polymer Microcapsules: Novel Tools for Biological and Pharmacological Applications. Small 2007, 3, 944-955. [4] Richardson, J. J.; Björnmalm, M.; Caruso, F. Technology-Driven Layer-by-Layer Assembly of Nanofilms. Science 2015, 348, 411-423. [5] Mo, R.; Tung, S. O.; Lei, Z.; Zhao, G.; Sun, K.; Kotov, N. A. Pushing the Limits: 3D Layer-byLayer-Assembled Composites for Cathodes with 160 C Discharge Rates. ACS Nano 2015, 9, 5009-5017. [6] Caruso, F.; Caruso, R. A.; Möhwald, H. Nanoengineering of Inorganic and Hybrid Hollow Spheres by Colloidal Templating. Science 1998, 282, 1111-1114. [7] Ye, C.; Kulkarni, D. H.; Dai, H.; Tsukruk, V. V. Programmable Arrays of “Micro-Bubble” Constructs via Self-Encapsulation. Adv. Funct. Mater. 2014, 24, 4364-4373. [8] Andres, C. M.; Larraza, I.; Corrales, T.; Kotov, N. A. Nanocomposite Microcontainers. Adv. Mater. 2012, 24, 4597-4600. [9] Breger, J. C.; Yoon, C.; Xiao, R.; Kwag, H. R.; Wang, M. O.; Fisher, J. P.; Nguyen, T. D.; Gracias, D. H. Self-Folding Thermo-Magnetically Responsive Soft Microgrippers. ACS Appl. Mater. Interfaces 2015, 7, 3398-3405. [10] Ye, C.; Shchepelina, O.; Calabrese, R.; Drachuk, I.; Kaplan, D. L.; Tsukruk, V. V. Robust and Responsive Silk Ionomer Microcapsules. Biomacromolecules 2011, 12, 4319-4325. [11] Köhler, K.; Möhwald, H.; Sukhorukov, G. B. Thermal Behavior of Polyelectrolyte Multilayer Microcapsules: 2. Insight into Molecular Mechanisms for the PDADMAC/PSS System. J. Phys. Chem. B 2006, 110, 24002-24010. [ 12 ] Elsner, N.; Kozlovskaya, V.; Sukhishvili, S. A.; Fery, A. pH-Triggered Softening of Crosslinked Hydrogen-Bonded Capsules. Soft Matter 2006, 2, 966-972. [13] Ariga, K.; Ji, Q.; Richards, Q. J.; Hill, J. P. Soft Capsules, Hard Capsules, and Hybrid Capsules. Soft Materials 2012, 10, 387-412. [14] Terentyeva, T. G.; Matras, A.; Rossom, W. V.; Hill, J. P.; Ji, Q.; Ariga, K. Bioactive FlakeShell Capsules: Soft Silica Nanoparticles for Efficient Enzyme Immobilization. J. Mater. Chem. B 2013, 1, 3248-3256. [ 15 ] Ye, C.; Combs, Z. A.; Calabrese, R.; Dai, H.; Kaplan, D. L.; Tsukruk, V. V. Robust Microcapsules with Controlled Permeability from Silk Fibroin Reinforced with Graphene Oxide. Small 2014, 10, 5087-5097. [16] Fernandes, P. A.; Delcea, M.; Skirtach, A. G.; Möhwald, H.; Fery, A. Quantification of Release from Microcapsules upon Mechanical Deformation with AFM. Soft Matter 2010, 6, 1879-1883.


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

20

Page 20 of 22 9/25/2015

[17] Decher,G.; Schlenoff, J. Multilayer Thin Films, Wiley-VCH, Weinheim, 2012. [18] Lvov, Y.; Möhwald, H.; Dekker, M. Protein Architecture: Interfacial Molecular Assembly and Immobilization Biotechnology, New York, 2000. [19] Jiang, C.; Tsukruk, V. V. Freestanding Nanostructures via Layer-by-Layer Assembly. Adv. Mater. 2006, 18, 829-840. [20] Ariga, K.; Yamauchi, Y.; Rydzek, G.; Ji, Q.; Yonamine, Y.; Wu, K. C.-W.; Hill, J. P. Layer-byLayer Nanoarchitectonics: Invention, Innovation, and Evolution. Chem. Lett. 2015, 43, 3668. [21] Kozlovskaya, V.; Kharlampieva, E.; Mansfield, M. L.; Sukhishvili, V. Poly(methacrylic acid) Hydrogel Films and Capsules: Response to pH and Ionic Strength, and Encapsulation of Macromolecules. Chem. Mater. 2006, 18, 328-336. [22] Shchepelina, O.; Drachuk, I.; Gupta, M. K.; Lin, J.; Tsukruk, V. V. Silk-on-Silk Layer-byLayer Microcapsules. Adv. Mater. 2011, 23, 4655-4660. [23] Quinn, J. F.; Caruso, F. Facile Tailoring of Film Morphology and Release Properties Using Layer-by-Layer Assembly of Thermoresponsive Materials. Langmuir 2004, 20, 20-22. [24] Kozlovskaya, V.; Kharlampieva, E.; Drachuk, I.; Cheng, D.; Tsukruk, V. V. Responsive Microcapsule Reactors Based on Hydrogen-Bonded Tannic Acid Layer-by-Layer Assemblies. Soft Matter 2010, 6, 3596-3608. [25] Yi. Q.; Wen, D.; Sukhorukov, G. B. UV-Cross-Linkable Multilayer Microcapsules Made of Weak Polyelectrolytes. Langmuir 2012, 28, 10822-10829. [ 26 ] Xu, W.; Choi, I.; Plamper, F. A.; Synatschke, C. V.; Müller, A. H. E.; Tsukruk, V. V. Nondestructive Light-Initiated Tuning of Layer-by-Layer Microcapsule Permeability. ACS Nano 2013, 7, 598-613. [27] Xu, V.; Choi, I.; Plamper, F. A.; Synatschke, C. V.; Müller, A. H. E.; Melnichenko, Y. B.; Tsukruk, V. V. Multicompartmental Microcapsules from Star Copolymer Micelles. Macromolecules 2014, 47, 2112-1436. [28] Zhu, Z.; Sukhishvili, S. A. Temperature-Induced Swelling and Small Molecule Release with Hydrogen-Bonded Multilayers of Block Copolymer Micelle. ACS Nano 2009, 3, 3595-3605. [29] Yi, Q.; Sukhorukov, G. B. Externally Triggered Dual Function of Complex Microcapsules. ACS Nano 2013, 7, 8693-8705. [30] Shchepelina, O.; Lisunova, M. O.; Drachuk, I.; Tsurkuk, V. V. Morphology and Properties of Microcapsules with Different Core Releases. Chem. Mater. 2012, 24, 1245-1254. [31] Habibi, Y.; Lucia, L. A.; Rojas, O. J. Cellulose Nanocrystals: Chemistry, Self-Assembly, and Applications. Chem. Rev. 2010, 110, 3479-3500. [ 32 ] Klemm, D.; Kramer, F.; Moritz, S.; Lindström, T.; Ankerfors, M.; Gray, D.; Dorris, A. Nanocelluloses: A New Family of Nature-Based Materials. Angew. Chem. 2011, 50, 54385466. [33] Moon, R. J.; Martini, A.; Nairn, J.; Simonsen, J.; Youngblood, J. Cellulose Nanomaterials Review: Structure, Properties and Nanocomposites. Chem. Soc. Rev. 2011, 40, 3941-3994. [34] Hu, L.; Zheng, G.; Yao, J.; Liu, N.; Weil, B.; Eskilsson, M.; Karabulut, E.; Ruan, Z.; Fan, S.; Bloking, J. T.; et al. Transparent and Conductive Paper from Nanocellulose Fibers. Energy Environ. Sci. 2013, 6, 513-518.


Page 21 of 22

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano CNC_MCs

21

9/25/2015

[35] Saito, T.; Kuramae, R.; Wohlert, J.; Berglund, L. A.; Isogai, A. An Ultrastrong Nanofibrillar Biomaterial: the Strength of Single Cellulose Nanofibrils Revealed via Sonication-Induced Fragmentation. Biomacromolecules 2013, 14, 248-253. [36] Lin, N.; Huang, J.; Sufresne, A. Preparation, Properties and Applications of Polysaccharide Nanocrystals in Advanced Functional Nanomaterials: A Review. Nanoscale 2012, 4, 32743294. [37] Mohanta, Y.; Madras, G.; Patil, S. Layer-by-Layer Assembled Thin Films and Microcapsules of Nanocrystalline Cellulose for Hydrophobic Drug Delivery. ACS Appl. Mater. Interfaces 2014, 6, 20093-20101. [ 38 ] Kargarzadeh, H.; Sheltami, R. M.; Ahmad, I.; Abullah, I.; Dufresne, A. Cellulose Nanocrystal: A Promising Toughening Agent for Unsaturated Polyester Nanocomposite. Polymer 2015, 56, 346-35. [39] Oh, S. Y.; Yoo, D.; Shin, Y.; Seo, G. FTIR Analysis of Cellulose Treated with Sodium Hydroxide and Carbon Dioxide. Carbohydrate Research 2005, 340, 417-428. [ 40] Farah, F.; Iwamoto, S.; Hori, N.; Iwata, T.; Takemura, A. Effect of Preacid-Hydrolysis Treatment on Morphology and Properties of Cellulose Nanowhiskers from Cocomut Husk. Cellulose 2011, 11, 443-450. [41] Nishiyama, Y.; Sugiyama, J.; Chanzy, H.; Langan, P. Crystal Structure and Hydrogen Bonding System in Cellulose Iα from Synchrotron X-ray and Neutron Fiber Diffraction. J. Am. Chem. Soc. 2003, 125, 14300-14306. [42] Sukhishvili, S. A. Layered, Erasable Polymer Multilayers Formed by Hydrogen-Bonded Sequential Self-Assembly. Macromolecules 2002, 35, 301-310. [43] Socrates, G. Infrared and Raman Characteristic Group Frequencies: Tables and Charts, John Wiley & Sons, New York, 2001. [44] Peng, Y.; Gardner, D. J.; Han, Y. Drying Cellulose Nanofibrils: in Search of a Suitable Method. Cellulose 2012, 19, 91-102. [45] Parthasarathi, R.; Bellesia, G.; Chundawat, S. P. S.; Dale, B. E.; Langan, P.; Gnanakara, S. Insights into Hydrogen Bonding and Stacking Interactions in Cellulose. J. Phys. Chem. A 2011, 115, 14191-14202. [46] Laugel, N.; Betscha, C.; Winterhalter, W.; Voegel, V.; Schaaf, P.; Ball, V. Relationship between the Growth Regime of Polyelectrolyte Multilayers and the Polyanion/Polycation Complexation Enthalpy. J. Phys. Chem. B. 2006, 110, 19443-19449. [47] Porcel, C.; Lavalle, Ph.; Ball, V.; Decher, G.; Senger, B.; Voegel, V.; Schaaf, P. From Exponential to Linear Growth in Polyelectrolyte Multilayers. Langmuir 2006, 22, 4376-4383. [48] Jiang, C.; Wang, C.; Gunawidjaja, R.; Lin, Y. H.; Gupta, M.; Kaplan, D. L.; Naik, R. R.; Tsukruk, V. V. Mechanical Properties of Robust Ultrathin Silk Fibroin Films. Adv. Funct. Mater. 2007, 17, 2229-2237. [49] Wang, Y.; Caruso, F. Mesoporous Silica Spheres as Supports for Enzyme Immobilization and Encapsulation. Chem. Mater. 2005, 17, 953-961. [50] Caruso, F. Hollow Capsule Processing through Colloidal Templating and Self-Assembly. Chem. Eur. J. 2000, 6, 413-419. [51] Boulmedais, V.; Frisch, B.; Etienne, O.; Lavalle, V.; Picart, C.; Ogier, V.; Voegel, J. C.; Schaaf, P.; Egles, C. Polyelectrolyte Multilayer Films with Pegylated Polypeptides as A


ACS Nano

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CNC_MCs

22

Page 22 of 22 9/25/2015

New Type of Anti-Microbial Protection for Biomaterials. Biomaterials 2004, 25, 2003-2011. [52] Lisunova, M. O.; Drachuk, I.; Shchepelina, O. A.; Anderson, K. D.; Tsukruk, V. V. Direct Probing of Micromechanical Properties of Hydrogen-Bonded Layer-by-Layer Microcapsule Shells with Different Chemical Compositions. Langmuir 2011, 27, 11157-11165. [53] Altaner, C. M.; Thomas, L. H.; Fernandes, A. N.; Jarvis, M. C. How Cellulose Stretches: Synergism between Covalent and Hydrogen Bonding. Biomacromolecules 2014, 15, 791798. [ 54 ] Sukhorukov, G. B.; Antipov, A. A.; Voigt, A.; Donath, E.; Möhwald, E. pH-Controlled Macromolecule Encapsulation in and Release from Polyelectrolyte Multilayer Nanocapsules. Macromol. Rapid Commun. 2001, 22, 44-46. [55] Ehmann, H. M. A.; Mohan, T.; Koshanskaya, M.; Scheicher, S.; Breitwieser, D.; Ribitsch, V.; Stana-Kleinschek, K.; Spirk, S. Design of Anticoagulant Surfaces Based on Cellulose Nanocrystals. Chem. Comm., 2014, 50, 13070-13072. [56] Mendelsohn, J. D.; Barrett, C. J.; Chan, V. V.; Pal, A. J.; Mayes, A. M.; Rubner, M. F. Fabrication of Microporous Thin Films from Polyelectrolyte Multilayers. Langmuir 2000, 16, 5017-5023. [57] Kozlovskaya, V.; Sukhishvili, S. A. Amphoteric Hydrogel Capsules: Multiple Encapsulation and Release Routes. Macromolecules 2006, 39, 6191-6199. [58] Petridis, L.; O’Neill, H. M.; Johnsen, M.; Fan, B.; Schulz, R.; Mamontov, E.; Marana, J.; Langan, P.; Smith, J. C. Hydration Control of the Mechanical and Dynamical Properties of Cellulose. Biomacromolecules 2014, 15, 4152-4159. [ 59 ] Fang, F.; Catchmark, J. M. Structure Characterization of Native Cellulose during Dehydration and Rehydration. Cellulose 2014, 21, 3951-3963. [60] Sun, B.; Hou, Q.; Liu, Z.; Ni, Y. Sodium Periodate Oxidation of Cellulose Nanocrystal and Its Application as A Paper Wet Strength Additive. Cellulose 2015, 22, 1135-1146. [61] Kozlovskaya, V.; Kharlampieva, E.; Jones, K.; Lin, Z.; Tsukruk, V. V. pH-Controlled Assembly and Properties of LbL Membranes from Branched Conjugated Poly(alkoxythiophene sulfonate) and Various Polycations. Langmuir 2010, 26, 7138-7147. [62] Shimizu, K.; Cha, J.; Stucky, G. D.; Morse, D. E. Silicatein α: Cathepsin L-like Protein in Sponge Biosilica. Proc. Natl. Acad. Sci. USA 1998, 95, 6234-6238. [63] Wang, Y. J.; Caruso, F. Enzyme Encapsulation in Nanoporous Silica Spheres. Chem. Commun. 2004, 13, 1528-1529. [64] Tsukruk, V. V.; Reneker, D. H. Scanning Probe Microscopy of Organic and Polymeric Films: from Self-Assembled Monolayers to Composite Multilayers. Polymer 1995, 36, 1791-1808. [65] Elsner, N.; Dubreui, F.; Fery, A. Tuning of Microcapsule Adhesion by Varying the Capsulewall Thickness. Physical Review E 2004, 69, 031802/1. [66] Mcconney, M. E.; Singamaneni, S.; Tsukruk, V. V. Probing Soft Matter with the Atomic Force Microscopies: Imaging and Force Spectroscopy. Polymer Reviews 2010, 50, 235-286. [67] Kharlampieva, E.; Slocik, J. M.; Singamaneni, S.; Poulsen N.; Krӧger, N.; Naik, R. R.; Tsukruk, V. V. Protein-Enabled Synthesis of Monodisperse Titania Nanoparticles on and within Polyelectrolyte Matrices. Adv. Funct. Mater. 2009, 19, 2303-2311.


Cellulose Nanocrystal Microcapsules as Tunable Cages for Nano

Recommend Documents