Elsevier

Biomaterials

Volume 31, Issue 3, January 2010, Pages 438-448
Biomaterials

The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function

https://doi.org/10.1016/j.biomaterials.2009.09.060Get rights and content

Abstract

The interaction between nanoparticles (NPs) and cells has been studied extensively, but the effect of particle shape on cell behavior has received little attention. Herein three different shaped monodisperse mesoporous silica nanoparticles (MSNs) of similar particle diameter, chemical composition and surface charge but with different aspect ratios (ARs, 1, 2, 4) were specially designed. Then the effects of particle shape of these three different shaped particles on cellular uptake and behavior were studied. The results indicated that these different shaped particles were readily internalized in A375 human melanoma (A375) cells by nonspecific cellular uptake. Particles with larger ARs were taken up in larger amounts and had faster internalization rates. Likewise, it was also found that particles with larger ARs had a greater impact on different aspects of cellular function including cell proliferation, apoptosis, cytoskeleton formation, adhesion and migration. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. Therefore, our findings may provide useful information for the development of new strategies for the design of efficient drug delivery nanocarriers and therapeutic systems and provide insights into nanotoxicity.

Introduction

The design of smart functional nanosystems for intracellular imaging and therapeutic applications requires a thorough understanding of the mechanisms by which nanoparticles (NPs) enter cells. Recently, a number of studies have focused on the interaction between NPs and biological systems in order to understand their trafficking at the systemic and cellular levels [1]. As is well documented, NPs can be transported into cells through a process called endocytosis [2]. In particular, pinocytosis occurs in all cell types and is mediated by at least four basic mechanisms: macropinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin–caveolae and dynamin-independent endocytosis [3]. The endocytotic process occurs through either specific or nonspecific cellular uptake depending on the surface properties of NPs. In biological and clinical applications, the ability to control and manipulate the accumulation of NPs inside a cell by specific cellular uptake makes it possible to improve diagnostic sensitivity and therapeutic efficiency [4]. However, a number of studies have demonstrated that the interaction between NPs and cell membranes can proceed by nonspecific cellular uptake, which should not be ignored [5], [6].

Recent observations in biological systems suggest that physical parameters of NPs, like size, shape and surface charge, can affect their nonspecific uptake into cells, and furthermore this nonspecific uptake of NPs can potentially induce cellular responses [7], [8], [9], [10]. Particle shape has been considered to play an important role in both cellular interactions with NPs and the systemic distribution of NPs. Worm-like magnetic NPs, for example, represent an improved nanomaterial platform for targeting and imaging tumors in vivo, and facilitate more efficient delivery of therapeutics to biological targets because of their large surface area, multiple attachment points, and long blood half-life [11]. However, people still have limited information regarding the effects of particle shape on cellular responses, such as cell proliferation, apoptosis, adhesion, migration and cytoskeleton formation. Therefore, investigating how the uptake of different shaped particles affects cell functions will assist in the design of nanoscale delivery systems and open up new NP bioapplications.

Mesoporous silica nanoparticles (MSNs), with a high BET surface area, large pore volume, uniform porosity, stable aqueous dispersion, excellent biocompatibility and in vivo biodegradability [12], are emerging as ideal agents for biomedical applications [13]. Encapsulation of therapeutic agents in MSNs has already been successfully used in the development of new drug carriers [14]. Moreover, some nonspherical MSNs have shown some superiorities in biomedical applications. For example, rod-like multifunctional mesoporous silica nanomaterials display great potential in monitoring cell trafficking, cancer cell metastasis and drug/DNA delivery [15]. In this study, we have studied the effect of different shaped MSNs on cellular behavior. First, different shaped MSNs, (spheres, and short and long rods), were fabricated and functionalized with fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC) for imaging and quantification of MSN uptake. Next, the ability of different shaped MSNs to be transported into model A375 cells was compared, and then the effects of different shaped MSNs on cell proliferation, apoptosis, adhesion, migration and cytoskeleton formation were investigated.

Section snippets

Materials

Cetyltrimethylammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), aqueous ammonia (NH3·H2O), dimethylformamide (DMF), 3-aminopropyl triethoxysilane (APTES), rhodamine B isothiocyanate (RITC) and fluorescein isothiocyanate (FITC) were obtained from Beijing Chemical Reagents Company (China). Dulbecco's modified Eagle's medium (DMEM) and fetal bovine serum (FBS) were from Gibco. Bovine serum albumin (BSA), Triton X-100 and 3-[4, 5-dimethylthiazolyl-2]-2, 5-diphenyltetrazolium bromide (MTT)

Fabrication and characterization of different shaped MSNs

We designed a series of MSNs with varying shape but the same diameter, chemical composition and surface charge by co-condensation under diluted TEOS and low surfactant conditions with aqueous ammonia as a catalyst. Different shaped MSNs were fabricated by controlling the concentration of reaction reagents in this reaction. Here, we chose the following three types of MSNs with distinct aspect ratios (ARs) to analyze the effects of particle shape on cellular functions in A375 cells: a

Discussion

Recently, a number of studies have focused on the interaction between NPs and biological systems in order to understand their trafficking at the cellular and systemic level and to develop new strategies for the design of efficient drug-delivery nanocarriers. Due to different interactions between NPs and cells, the ability of different NPs to penetrate the cell membrane may vary. NPs are transported into the cell by specific or nonspecific cellular uptake mechanisms depending on the surface

Conclusions

In summary, we have demonstrated that MSNs of well-defined shape are internalized by nonspecific cellular uptake and have an influence on cell behavior including protein expression. These findings provide strong evidence that nanostructures not only passively interact with cells, but also actively engage and mediate the molecular processes that are essential for regulating cell functions. In addition, our data also demonstrate the relationship between MSN shape and cellular responses such as

Acknowledgements

The authors acknowledge financial support from the National Hi-Technology Research and Development Program (“863” Program) (2007AA021803 and 2009AA03z322), the National Natural Science Foundation (No. 60736001), and the National Basic Research Program (“973” Program) of China (No. 2006CB932601).

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