Letter pubs.acs.org/macroletters
Large-Scale Synthesis of Monodisperse Red Blood Cell (RBC)-Like Polymer Particles Delong Xie, Xiaolin Ren, Yuhui Xie, Xinya Zhang,* and Shijun Liao School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China S Supporting Information *
ABSTRACT: Red blood cell (RBC)-like particles have shown great interest as a model for the understanding of the cell behavior and as promising biomaterials in targeted drug delivery. In this study, a simple and versatile route was proposed for the large-scale synthesis of monodisperse and well-defined RBC-like PS particles using divinylbenzene (DVB) as the cross-linker and ethanol as reaction medium. RBC-like particles were obtained due to the asymmetric shrinkage of a cross-linked network during the phase separation process. An ordered self-assembly monolayer with the concave facing up at the air−water interface was also demonstrated. cross-linkers or fluorescent agents,11 DVB used as cross-linked agent was introduced into the reaction system after the nucleation stage finished. Well-defined RBC-like particles have been obtained by individually adjusting the feeding method of DVB or the polarity of the reaction medium. Moreover, these RBC-like particles were able to form ordered monolayer film through rapid self-assembly with the concave facing up at the air−water interface, which promised them with a potential application in photonic crystal. As shown in Figure 1, nonspherical PS particles with RBClike morphology were obtained when DVB was introduced, while monodisperse spherical PS particles could be prepared without the addition of DVB. Knobby RBC-like PS particles with many nodes on the particle surface were observed when 1% DVB was added in 3 h (Figure 1b). If we delay the feeding time of DVB to 5 h, particle morphology kept RBC-like but those small nodes disappeared and several dimples generated on the particle surface (Figure 1c). Figure 2 showed the possible formation mechanism of RBC-like PS particles. During the dispersion polymerization, precipitated P(DVB-St) nuclei move to the surface of growing PS particles and further develop into a cross-linked network. The uniformity of network critically depends on the distribution of P(DVB-St) nuclei. The unreacted monomers prefer to diffuse into the growing PS particles. This process is usually interfered by the cross-linked network. Because of the incompatibility between St monomer and the newly formed network, phase separation happens and the swollen St monomers are driven to those zones where the blend is allowed in terms of thermodynamics.12 This heterogeneous separation process exerted a serious influence
R
ecently, researchers have shown an enormous interest in the design and synthesis of nonspherical and anisotropic particles due to their promising applications in Janus surfactant,1 functional coatings,2 biological sensors,3 anisotropic photonic crystals,4 and drug carriers.5 One of the key interests is the red blood cell (RBC)-like particle with a concave morphology. Although the diameter of RBC is much larger than capillary blood vessels, it can flow through capillaries and circulate long-term in the human body due to its ability to deform and squeeze through restrictions in the vasculature and then recover to its initial shape after passing through capillaries.5a,6 These unique physical and chemical properties in terms of size, shape, flexibility, and chemical composition are essential to their biological functions.6b Inspired by the unique ability of this cell, researchers seek to design and synthesize RBC-like particles to perform important and complex tasks in the biological entities.1,5a,6,7 Therefore, artificial fabrication of RBC-like particles could advance the frontier of functional materials. Generally, three approaches have been developed to synthesize nonspherical colloidal particles, including deformation of spherical particles,8 lithography combining with microfluidics,3,9 and emulsion polymerization.7a,10 However, the above fabrications of RBC-like particles can be either tedious or only get nanosized particles, while RBC-like particles prepared in low-polar or nonpolar medium were rarely reported. Herein, we described a simple and versatile route to prepare monodisperse and well-defined cross-linked RBC-like polymer particles through one−pot dispersion polymerization, where ethanol or the mixture of ethanol and water was used as reaction medium. To verify its feasibility, we have applied it to RBC-like polystyrene (PS) particles. These RBC-like particles could be synthesized with large-scale by this approach. Since the nucleation stage of dispersion polymerization is very sensitive and vulnerable to some functional monomers such as © XXXX American Chemical Society
Received: November 25, 2015 Accepted: January 11, 2016
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DOI: 10.1021/acsmacrolett.5b00852 ACS Macro Lett. 2016, 5, 174−176
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ACS Macro Letters
ethanol/water would elevate the solvent polarity and shorten the critical chain length of PS.14 Consequently, nuclei number increased and average particle size decreased (Figure 1e). However, a higher solvent polarity was not conducive to the formation of RBC-like particle. The increase of PS nuclei would significantly impair the cross-linking density and the degree of phase separation. Thus, deformation disappeared and only spherical particles were observed. This was proved by tuning the mass ratio to 8:2 (Figure 1f). According to the mechanism of dispersion polymerization, precipitated P(DVB-St) nuclei move to the surface of growing PS particles and further develop into a cross-linked network. The uniformity of network critically depends on the distribution of P(DVB-St) nuclei on the PS core particles which can be controlled by the feeding time of DVB. Based on our previous speculation, spherical cross-linked particles can be produced if the distribution of P(DVB-St) nuclei is uniform. Considering the half-life of AIBN is about 5 h at 70 °C,15 the concentration of free radical would drop drastically after the reaction running for 5 h. That is, DVB is likely to be captured by the free radicals on the growing PS particle surface if it is fed at that moment. This is equivalent to change the nucleation site of P(DVB-St), which facilitates the uniformity of cross-linked network. Correspondingly, particle shape changed from RBClike to polyhedron-like and finally sphere-like (Figure 3). These results were exactly consistent with our speculation. Figure 1. SEM images PS particles with different morphology, (a) spherical, (b) knobby RBC-like, (c) dimply RBC-like, (d) apple-like, which were prepared in ethanol, and PS particles prepared at different mass ratio of ethanol/water: (e) 9:1; (f) 8:2.
Figure 2. Schematic illustration for the possible formation mechanism of RBC-like PS particles.
on the growth of particles.2d,13 Though particle size gradually increased with the polymerization of swelling St monomer, the growth of highly cross-linked region inside particles was much slower than the others. Particle surface was forced to distort and cavities or dimples were finally formed in situ (Figure 1c). Moreover, the cross-linked network tended to be more uniform at a faster feeding mode of DVB, thus the high cross-linked and low cross-linked region alternately distributed on the particle bulge, leading to the generation of small nodes (Figure 1b). The cross-linked network became extremely compact when the concentration of DVB increased to 6%, making it difficult for St monomer to enter into the particle. As a result, secondary nucleation occurred and average particle size decreased. The declined swelling capacity of particles also impaired the degree of phase separation. Therefore, visible deformation decreased and only a shallow cave appeared on particle surface, forming apple-like particles (Figure 1d). In order to understand the effect of solvent polarity on the morphology of particles, water was introduced to the system to replace partial ethanol as solvent, and it was found that a decreased mass ratio of
Figure 3. SEM images of PS particles with different feeding time of 2% DVB: (a) 1.5, (b) 5, (c) 7, and (d) 9 h.
The common self-assembly methods, such as gravity deposition, vertical deposition, and convective self-assembly, are usually applicable to nanoparticles. Nevertheless, those methods would not work for microlevel particles, as their sedimentation rate is larger than the solvent evaporation rate. We presented a facile method to assemble microsized RBC-like particles at the air−water interface. Since the effective density of PS monolayer film was lower than the density of water, PS particles were capable of floating on the water surface when PS suspension was added into the Petri dish.16 The gravity center of RBC-like particles located in the bulge region due to their shape asymmetry. Hence, particle concave was favorable to face up to keep its own stability. With the evaporation of water, the floating PS particles packed more closely under the induction of vertical capillary force. SEM images of the monolayer film 175
DOI: 10.1021/acsmacrolett.5b00852 ACS Macro Lett. 2016, 5, 174−176
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ACS Macro Letters
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formed by RBC-like particles were illustrated in Figure 4. RBClike particles were neatly arranged and their concave was all pointing up, which reflected the good monodispersity of PS particles.
Figure 4. SEM images of monolayer film formed by RBC-like PS particles.
We demonstrate a simple and versatile route for the largescale synthesis of monodisperse and well-defined RBC-like PS particles by one-pot dispersion polymerization. Particle morphology was primarily affected by the concentration or feeding manner of DVB and the ethanol/water mass ratio. These nonspherical particles were the products of heterogeneous phase separation between the uneven cross-linked network and St monomers. In addition, RBC-like particles were able to form ordered monolayer film through rapid selfassembly at the air−water interface, which promised them with a potential application in photonic crystal.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.5b00852. Materials and synthesis details (PDF).
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors gratefully acknowledge the financial support from the Science and Technology Planning Project of Guangdong Province, China (2015A010105008).
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REFERENCES
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DOI: 10.1021/acsmacrolett.5b00852 ACS Macro Lett. 2016, 5, 174−176
