Size-controlled synthesis, characterization, and cytotoxicity study of monodisperse poly(dimethylsiloxane) nanoparticles

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Abstract

Polydimethylsiloxane (PDMS) nanoparticles (NPs) were synthesized using dimethylsiloxane and tetraethyl orthosilicate as precursors via a modified Stöber process. A diluted ammonia solution was added to the reaction mixture. This induced base-catalyzed hydrolysis and condensation, forming dispersed nanocolloids. The as-synthesized organosilica NPs exhibited excellent colloidal stability without any noticeable precipitation in water. The particle size was readily tunable, in a diameter range of approximately 50–300 nm, by changing the amount of catalysts added to the reaction. Furthermore, we evaluated the cytotoxicity of PDMS NPs using a CCK-8 assay to demonstrate that PDMS NPs are promising for biomedical applications.

Introduction

Colloidal inorganic nanoparticles (NPs) have been extensively studied in biomedical applications and clinical medicine [1]. Among various types of nanomaterials, silica NPs have attracted significant attention for various applications, including bioimaging [2], drug or gene delivery carriers [3], [4], and enzyme immobilizations [5]. Silica NPs exhibit great design flexibility, including size and shape tunability from the nanometer scale to the micrometer scale, and facile surface functionalization via silane chemistry [6]. Large-scale synthesis of silica NPs is possible at a low cost, which facilitates the commercial application of silica NPs. The silica matrix exhibits a low cytotoxicity and high chemical stability, thus making silica NPs a promising platform for biomedical applications [7]. In addition, the silica matrix can be used as overcoating moieties for the fabrication of functional hybrid inorganic NPs with core–shell architectures using semiconducting quantum dots [8], plasmonic metals [9], and magnetic NPs [10] as a core to reduce the toxicity of the inorganic NPs while enhancing the capability for surface functionalization [11].

Although biosafety evaluations of crystalline, micron-size silica particles are well-documented [12], [13], recent studies reveal that reducing the size of colloidal amorphous silica NPs to the nanoscale can induce toxicity in in vitro and in vivo applications [14], [15], which are highly dependent on the particle sizes, surface chemistry, geometry, and porosity [16], [17]. Therefore, developing a method to synthesize colloidal NPs that exhibit lower toxicity or non-toxicity at a nanoscale size as well as superior design flexibility and the capability for facile functionalization is highly desirable for utilizing these biocompatible nanocarriers as multifunctional platforms [18], [19]. Siloxane-based organosilica NPs are an inorganic–organic hybrid material fabricated by the homogeneous incorporation of organosilicon groups in the silica framework [20], [21]. The structural moiety of organosilica is similar to that of silica NPs, except that organic groups are directly incorporated into silica frameworks via covalent linkages [20]. Therefore, functional organic groups can be easily changed by using different types of organosilicon precursors, thus enabling the properties and functions of organosilica NPs to be easily tailored. Organosilica frameworks are considered to be highly biocompatible [22], [23], making them ideal candidates for potential nanocarriers for biomedical applications. Although many studies have reported on the synthesis of organosilica NPs [7], [20], methods for synthesizing monodisperse NPs while tailoring their size and compositions and investigations of the cytotoxicity of organosilica NPs of various sizes and compositions are rare.

In this study, we demonstrated the size-controlled synthesis of colloidal poly(dimethylsiloxane) (PDMS) NPs using a modified Stöber process. The PDMS framework was composed of organosilicon-containing dimethylsiloxane groups, which are extensively used in biomedical applications owing to their superior chemical stability, inertness, flexibility, and excellent biocompatibility [24]. Monodisperse spherical PDMS NPs were synthesized via base-catalyzed hydrolysis and condensation in a reaction mixture of dimethydiethoxylsiloxane (DMDES) and tetraethyl orthosilicate (TEOS) precursors. The size of the monodisperse NPs was tuned in the diameter range of 80–350 nm by changing the ratio of the concentration of ammonia catalysts to the total concentration of precursors. The composition of DMDES and TEOS in the NP framework was tuned by changing the amount of precursors added to the reaction mixture while maintaining the size uniformity. Synthesized NPs of various sizes and compositions exhibited excellent colloidal stability without any noticeable precipitation in water, which reveals the potential of our PDMS NPs for use in biomedical applications. Finally, we investigated the size and composition-dependent toxicity of the PDMS NPs to understand their potential cytotoxicity effects.

Section snippets

Chemicals

DMDES (97.0%), TEOS (98.0%), and ethyl alcohol (ACS reagent, ≥99.5%), were purchased from Sigma–Aldrich. A 28% ammonia solution (NH4OH) was purchased from JUNSEI Chemical. Rhodamine B (RhB) was purchased from Fluka. All chemicals were used as received. Distilled water, which was used in all the reactions and for the cleaning of glassware, was purified to a resistance of 18 MΩ and filtered through a 0.22-μm membrane to remove any impurities.

Synthesis of siloxane-based PDMS NPs

Monodisperse uniform-sized siloxane-based PDMS NPs were

Results and discussion

Monodisperse colloidal PDMS NPs were synthesized via a modified Stöber method. Because DMDES precursors have two methoxy groups and condensation occurs along these alkoxide groups to form a linear polymeric chain, TEOS was added to cross-link these polymeric chains into the networks. A diluted ammonia solution was added to the reaction mixture containing DMDES and TEOS precursors with a molar ratio of 8:2 in ethanol and water solutions. The addition of ammonia induced base-catalyzed hydrolysis

Conclusions

The size-controlled synthesis of monodisperse siloxane-based colloidal PDMS NPs was demonstrated in this study. The size of the NPs was readily tuned in the diameter range of approximately 50–300 nm by changing the amount of ammonia added. The compositions of the NPs were tuned by changing the types of siloxane precursors used in the reaction. PDMS NPs exhibit superior colloidal stability in water without any aggregations. The cytotoxic effects of PDMS NPs of various sizes and compositions were

Acknowledgments

This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI14C3484, HI15C1744) and by the Development of Platform Technology for Innovative Medical Measurements Program from Korea research Institute of Standards and Science (KRISS—2016-16011064). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea

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