Subscriber access provided by University of Sussex Library
Article
Kinetically controlled dendritic mesoporous silica nanoparticles: from dahlia- to pomegranate-like structures by micelle filling Yue Wang, Hao Song, Yannan Yang, Yang Liu, Jie Tang, and Chengzhong Yu Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.8b02712 • Publication Date (Web): 03 Aug 2018 Downloaded from http://pubs.acs.org on August 8, 2018
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 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 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.
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 8 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
Chemistry of Materials
84x47mm (300 x 300 DPI)
ACS Paragon Plus Environment
Chemistry of Materials 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
Kinetically controlled dendritic mesoporous silica nanoparticles: from dahlia- to pomegranate-like structures by micelle filling Yue Wang, Hao Song, Yannan Yang, Yang Liu, Jie Tang and Chengzhong Yu* Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia ABSTRACT: A unique dynamic structural transition from large-pore dendritic mesoporous silica nanoparticles (DMSNs) with a dahlia-like morphology to pomegranate-like mesoporous silica nanoparticles (MSNs) with small mesopores is reported. The structural evolution is accompanied by gradually filling the preformed dendritic large pores with silica-coated micelles, providing a series of DMSNs with kinetically controlled dual mesoporosity. The heterogeneous porous structure of DMSNs demonstrates advantages in the co-loading of two positively charged drug molecules, showing promising potential in cellular delivery applications.
Since their discovery in early 1990s,1-3 mesoporous materials with ordered and controllable mesostructures,4-6 tunable compositions7-11 and variable morphologies7 have attracted much attention with various applications.12-15 Particularly, mesoporous silica nanoparticles (MSNs) with small particle sizes, good biocompatibility16 and easy surface modification12 have been extensively studied with applications in drug delivery17 and adsorption.18 Moreover, MSNs have been used as templates in the preparation of soft polymer and carbon based materials with broad applications.19-23Traditional MSNs such as SBA-1524 and MCM-4125 type materials have relatively small pore sizes. The successful synthesis of KCC-126 with both large dendritic pores (5-30 nm) and monodispersed uniform particle sizes (250-450 nm) has sparked significant interest in synthesis27-32 and applications of this new type of dendritic MSNs (DMSNs), specifically in the cellular delivery of various cargo molecules.27-28, 33-38 Significant progresses have been made in the structural control over DMSNs (e.g., particle size,30, 33, 38 pore size,29, 32, 36-37 bimodal pores29, 31, 36, 39) and their assembly strategies including biphasic synthesis,29 microemulsion templating,26, 31, 38 the aggregation of composite micelles in the presence of competing anions in aqueous systems,30, 32 and the assembly from lamellar subunits.33, 36-37 To date, these mechanisms are mainly focused on the formation of DMSNs as an end product. The structural heterogeneity of DMSNs controlled by reaction kinetics as well as its significance in the applications of DMSNs has been rarely reported. Herein, we report an unusual dynamic structural transition from DMSNs with a dahlia-like morphology (Scheme 1, A1) to pomegranate-like small-pore MSNs (A2) with the large dendritic pores gradually filled by silica-coated composite micelles (Scheme 1B). This new structural evolution mechanism has important implications. (1) DMSNs should be considered as a kinetically controlled product, with its structure changing with reaction time (B1 or B2). (2) B2 is not a “pure” structure neither, but represents a series of DMSNs, whose structure is dependent on not only the reaction time but also the structural evolution (from B1 to B3) time window that can be further controlled by other reaction parameters. In this regard, care should be taken on the significant impact of reaction kinetics on the final structures of DMSNs to allow for repro-
ducible synthesis and applications. (3) It is possible to generate DMSNs with similar particle sizes and dendritic pore sizes, but different amounts of small-sized mesopores (due to the removal of micelles) within the large dendritic pores. Such a heterogeneous dual-pore structure, as we will demonstrate in this work, provides unique opportunities using bare DMSNs in the co-delivery of two positively charged drug molecules for enhanced cellular delivery applications.
Scheme 1. From a dahlia-like (A1) DMSN to pomegranatelike (A2) MSN: a kinetic micelle filling mechanism (B). The dahlia-like DMSNs (B1) are firstly assembled by an anionassisted approach through lamellar building blocks. By gradually filling the large dendritic pores with composite micelles, a series of intermediate structures (B2) and small-pore MSNs with the dendritic pores completely filled (B3) are obtained. Objects are drawn not to scale. The structural transition from dahlia-like DMSNs to pomegranate-like MSNs was observed in an alkaline aqueous system utilizing tetraethylorthosilicate (TEOS) as the silica precursor, cetyltrimethylammonium bromide (CTAB) as the surfactant and trifluoroacetate anions (FC2) as co-templates. After vigorous stirring at different temperature (T, 80 or 60 °C), FC2/CTAB molar ratio (R, R=0.5-4) and time (t, t = 0.3-24 h), samples denoted MSNs-T-R-t were collected by centrifugation. The final products were obtained by calcination at 550 °C for 5 h in air to remove surfactants.
ACS Paragon Plus Environment
Page 2 of 8
Page 3 of 8 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
Chemistry of Materials The influence of reaction time on the final structures was firstly studied at a fixed T of 80 °C and R of 1. Transmission electron microscopy (TEM) images of MSNs-80-1-t samples (t = 0.3, 1, 2, 5 h) are shown in Figure 1A-D, respectively. MSNs80-1-0.3, MSNs-80-1-1 and MSNs-80-1-2 (Figure 1 A-C) all exhibit the typical center-radial dendritic pore structures reported in literature30, 37. However, with increasing t from 0.3 to 2 h, the mass thickness-contrast in the TEM images appears to increase significantly and the porous voids (air) are less apparent, suggesting that the silica distribution density over the porous space is increased. Surprisingly, the radial dendritic pore structure cannot be observed in MSNs-80-1-5 (Figure 1D), instead small mesopores similar to that of conventional MSNs40 are observed at a prolonged t of 5 h. The average particle size measured from TEM images is 129, 151, 163 and 166 nm for MSNs-80-1-0.3, MSNs-80-1-1, MSNs-80-1-2 and MSNs-80-1-5, respectively.
Figure 2. SEM images (A-D) of MSNs-80-1-t, t = 0.3, 1, 2 and 5 h, respectively. The corresponding Barrett-Joyner-Halenda (BJH) pore size distribution curves of MSNs-80-1-t calculated from the adsorption branch are shown in Figure S1B. For MSNs-80-1-0.3, MSNs-80-1-1 and MSNs-80-1-2, two peaks are observed, one centered at ~2 nm and another at ~20 nm from the center radial opening pores. The intensity of the peak at ~2 nm increases while that at ~20 nm decreases with t. For MSNs-80-1-5, the mesopore distribution at 2 nm becomes the main peak even the small mesopore volume is reduced to 0.06 cm3g-1, suggesting that most of the small mesopores are closed.42 The physical properties of MSNs-80-t are summarized in Table 1. With increasing t, the pore size decreases from 26.7 to 2.3 nm, the BET surface area decreases from 488 to 207 m2g-1, and the total pore volume decreases from 1.28 to 0.25 cm3g-1. Table 1. Physical properties of MSNs-80-1-t Figure 1. TEM images (A-D) of MSNs-80-1- t, t = 0.3, 1, 2 and 5 h, respectively. Scanning electron microscope (SEM) images of MSNs-80-1-t shown in Figure 2 further confirm the observation from TEM images. The large pore openings are observed directly in MSNs-80-1-0.3 (Figure 2A), MSNs-80-1-1 (Figure 2B) and MSNs-80-1-2 (Figure 2C), whereas the pore opening is reduced in size with increasing t. The small mesopores in MSNs-80-1-5 cannot be seen clearly in Figure 2D, showing a relatively smooth surface. The nitrogen sorption analysis was also conducted to characterize the pore structures of MSNs-80-1-t. The adsorption and desorption isotherms of MSNs-80-1-t are typical type IV. The major capillary condensation steps of MSNs-80-1-0.3, MSNs80-1-1 and MSNs-80-1-2 (Figure S1A) occur at high relative pressure (P/P0) of > 0.85, indicating the existence of large pores. For MSNs-80-1-5, two obvious capillary condensation steps are observed, one at P/P0 of 0.3-0.4 attributed to small mesopores and another at ~0.9 attributed to the inter-particle packing voids.41
Sample name
D /nm
MSNs-80-1-0.3 129
d /nm
S V /m2g-1 /cm3g-1
Vsp Vlp /cm3g-1 /cm3g-1
1.3, 26.7
488
1.28
0.12
0.67
MSNs-80-1-1
151
2.7, 23.1
373
0.78
0.15
0.33
MSNs-80-1-2
163
2.8, 21.9
334
0.69
0.23
0.21
MSNs-80-1-5
166
2.3
207
0.25
0.06
0
Note: D indicates the particle diameter, d represents the pore size, S refers to the surface area, V is the total pore volume, Vsp and Vlp are the accumulated pore volume of small (~ 2 nm) and large pores (~20 nm), respectively.
To get information on the internal structures, electron tomography (ET) analysis was employed to compare MSNs-80-10.3, MSNs-80-1-2 and MSNs-80-1-5. The tomogram sliced from the center of MSNs-80-1-0.3 (Figure 3A) clearly presents the large dendritic and open pores. The wall thickness is measured to be 3.8 nm, indicating the formation of dendritic pore by lamellar structures, which is consistent with a previous literature report.36 The dendritic structure with large pore
ACS Paragon Plus Environment
2
Chemistry of Materials 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
opening for MSNs-80-1-2 was indicated by black arrows in Figure 3B. The wall is irregular and thicker than MSNs-80-10.3 and that in previous reports.29, 36-37 There are small mesopores (~ 2 nm) found on the wall indicated by red arrows, in accordance with nitrogen sorption analysis results. For MSNs80-1-5, only small mesopores of ~ 2 nm, but not the large dendritic pores are observed. However, some concaved voids are observed at the boundary of particles (Figure 3C, black arrows) with shorter depth compared to MSNs-80-1-2. It is noted that small mesopores of ~ 2 nm cannot be clearly observed in MSNs-80-1-0.3, suggesting that the micropores of 1.3 nm should have a different origin compared to those of ~ 2 nm mesopores observed in MSNs-80-1-2 and MSNs-80-1-5.
Figure 3. ET slices of MSNs-80-1-t prepared for 0.3 h (A), 2 h (B) and 5 h (C) taken from the center of one particle, scale bar: 50 nm. The above results reveal a time-dependent structural transition from large-pore DMSNs to small-pore MSNs with the large dendritic pores gradually filled by small mesopores. The time window of the structural transformation from large-pore DMSNs to small-pore MSNs influenced by other parameters was further studied. The effect of R, which is one important parameter to induce the formation of DMSNs,33, 36-37 was investigated by adjusting R (R=0.5 and 4) while keeping the reaction temperature at 80 °C. Surprisingly, the dendritic pore structure was observed for MSNs-80-0.5-0.3 at an early reaction time point (Figure 4A), while the completed structural transformation was observed at 2 h (Figure 4B), faster than that in MSNs-80-1-t series (~ 5 h at a higher R of 1). The small-pore structure maintained up to 24 h (Figure 4C and 4D). In contrast, when R was increased to 4, the large-pore dendritic structure maintained in MSNs-80-4-t samples till 24 h (Figure 4E-H) while the small-pore structure could not be formed at this time point. The nitrogen sorption analysis of MSNs-80-4-24 supported the conclusion (Figure S2), where a bimodal pore size distribution (2.5 and 18.4 nm) is observed. Our study suggests that the time window of the structural transition from large-pore DMSNs to small-pore MSNs is positively correlated to the R values (higher R for a longer transition time, and vice versa).
Figure 4. TEM images of MSNs-80-0.5-t (A-D) andMSNs-
Page 4 of 8
80-4-t (E-H) obtained at various t, t= 0.3 h (A, E), 2 h (B, F), 5 h (C, G) and 24 h (D, H). The structural transition was further studied in MSNs-60-1-t series (R=1) when the reaction temperature was decreased to 60 °C. TEM images (Figure S3) revealed the formation of unilamellar vesicle-like subunits and then dendritic structures at 0.3-1 h (Figure S3A, B). However, small-pore MSNs could not be observed at prolonged reaction time till 24 h (Figure S3C and D) at 60 °C. Compared to the studies carried out at 80 °C (MSNs-80-1-t, Figures 1-3), it is shown that a lower temperature favors a longer time window of the structural transition from large-pore DMSNs to small-pore MSNs. A dynamic composite micelle filling mechanism is proposed to explain the structural transition from large-pore DMSNs and small-pore MSNs (Scheme 1). In our synthesis, the fluorinated trifluoroacetate anions (FC2) and cetyltrimethylammonium cations (CTA+) as well as silicate species (from TEOS hydrolysis and condensation) could form silica-coated spherical micelles (Figure S4) and/or lamellar structures (Figure S3A), the latter being the building block to form the DMSNs.36 However, even when the DMSNs were formed, e.g., in MSNs-80-1-1, composite micelles with an average diameter of ~ 5 nm43 were still observed in the supernatant (Figure S4). The co-existence of DMSNs and spherical micelles at the same time is important in understanding our micelle-filling mechanism. It is proposed that the gradual micelle filling into the void space of preformed large-pore DMSNs is responsible for the structural transition towards final smallpore MSNs. This mechanism can be used to explain the pore structure differences in various samples. For MSNs-80-1-0.3, the micropores of ~1.3 nm should be attributed to amorphous silica because there is little micelle filling at this early time. With increasing t to 1 and 2 h, the small mesopores (~ 2.7 nm) with increasing Vsp should come from the gradually filled silica-coated micelles and after surfactant removal. When t is prolonged to 5 h, the large dendritic pores are almost fully filled by silica coated micelles and possibly free silicate oligomers. Thus, even after calcination, most of the mesopores of ~ 2.3 nm embedded in the interior part of MSNs-80-1-5 are not accessible42, leading to the smallest surface area and pore volume among four samples. The micelle-filling mechanism can also be used to explain the impact of the ratio of FC2/CTA+ and reaction temperature on the structural transition, which will be discussed in the following section to compare our mechanism with reported formation mechanisms of DMSNs.29, 32, 36-37 (1) Kinetically controlled heterogenous structures of DMSNs. There are several reported formation mechanisms of DMSNs such as assembly by the silicate/surfactant/oil composites at the water-oil interface in biphasic29 and microemulsion systems,26, 31, 38 the competition effect of anions towards composite micelles in water systems,30, 32 and the growth of lamellar conic structures in our previous studies.33, 36-37 These mechanisms generally explain the final structures of DMSNs. The micelle-filling mechanism proposed in this study reveals that DMSNs have dynamically changing structures. The silicacoated micelles heterogeneously nucleate on preformed large dendritic pore surface due to further condensation between silanol groups, in accordance with our observations that the pomegranate-like structures cannot be reverted to dahlia-like structures (data now shown). The extent of micelles filled into the dendritic large pores has consequences on the heterogeneous structures of DMSNs: not only bimodal mesopores (co-
ACS Paragon Plus Environment
3
Page 5 of 8 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
Chemistry of Materials existence of large dendritic pores and small mesoporous generated from removing micelles), but also their fractions of small mesopore deposited inside the large dendritic pores could be changed over reaction time, thus DMSNs should not be considered as a thermodynamically stable product with a given structure. (2) The role of FC2. The unique role of FC2 in our reaction system is described from two aspects. Firstly, as previously reported, the use of FC2 together with CTA+ favors the formation of DMSNs33. Secondly but more importantly, FC2 has weaker capability to induce the formation of DMSNs than heptafluorobutyrate / perfluorooctanoate anions (evidenced by the formation of DMSNs at lower anions/ CTA+ ratios),33 leading to a reasonably short time window (e.g., 5 h) to observe the structural transition from DMSNs to small-pore MSNs. The impact of R values of FC2/CTA+ and reaction temperature on the structural transition time window (Figure 4) can be explained by the micelle-filling mechanism considering the interaction between FC2 and CTA+ micelles. A lower R value would result in less lamellar building blocks while more spherical micelles, thus a faster micelle filling kinetics (MSNs-80-0.5-t versus MSNs-80-1-t series). Similarly, a higher concentration of spherical micelles due to weakened electrostatic interaction between cationic and anionic molecules at elevated temperature44 contributes to a faster structural transition (MSNs-80-1-t compared with MSNs-60-1-t series). It is predicted that very high R values (e.g., >4), or low temperature, or the use of reagents with strong ability to induce micelle structural change, could result in further reduced concentration of spherical micelles, which are insufficient to fill in the dendritic voids completely within the commonly selected reaction time (
