中秋节怎么过
Accepted Manuscript
The shape effect of PEGylated mesoporous silica nanoparticles on cellular up‐
take pathway in Hela cells
Nanjing Hao, Linlin Li, Qiang Zhang, Xinglu Huang, Xianwei Meng, Yanqi
Zhang, Dong Chen, Fangqiong Tang, Laifeng Li
PII:S1387-1811(12)00351-4
DOI:dx.doi/10.1016/j.micromeso.2012.05.040
Reference:MICMAT 5567
To appear in:Microporous and Mesoporous Materials
Received Date:15 December 2011
统一资源定位符
Revid Date:29 May 2012
Accepted Date:30 May 2012
布丁英语Plea cite this article as: N. Hao, L. Li, Q. Zhang, X. Huang, X. Meng, Y. Zhang, D. Chen, F. Tang, L. Li, The shape effect of PEGylated mesoporous silica nanoparticles on cellular uptake pathway in Hela cells, Microporous and Mesoporous Materials (2012), doi: dx.doi/10.1016/j.micromeso.2012.05.040
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The shape effect of PEGylated mesoporous silica nanoparticles on cellular uptake pathway in Hela cells
面积的单位Nanjing Hao a,c, Linlin Li a, Qiang Zhang b, Xinglu Huang a, Xianwei Meng a, Yanqi Zhang a, Dong Chen a, Fangqiong Tang a,* and Laifeng Li a,*
a Technical Institute of Physics and Chemistry, Chine Academy of Sciences, Beijing 100190, P. R. China.
b The General Hospital of Chine People’s Liberation Army, Beijing 100853, P. R. China.
c Graduate School of the Chine Academy of Sciences, Beijing 100049, P. R. China.
谷雨的含义* Authors to whom any correspondence should be addresd. No.29 Zhongguancun East Road, Beijing, 100190, P. R. China. Tel./Fax: +86 10 82543521
E-mail address: tangfq@mail.ipc.ac or lfli@mail.ipc.ac
Abstract
The shape of nanoparticles plays an important role in the interaction between cells and particles, however, the shape effect of mesoporous silica nanoparticles on the cellular uptake pathway and mechanism has not been reported. Herein, three different kinds of fluorescent mesoporous silica nanoparticles (FMSN, aspect ratio=1, 2, and 4, ca. 100 nm in diameter) with similar fluorescent intensity at equivalent concentration were fabricated by a co-condensation strategy. In simulated body fluid (SBF), the PEGylated FMSN (FMSN-PEG) has higher dispersity and stability than非正常损失
the naked counterparts. So we cho the FMSN-PEG to rearch of shape effect on the cellular uptake pathway in Hela cells. We found that the uptake kinetics and pathway of three different shape
d FMSN-PEG were obviously shape-dependent. The long-rod FMSN-PEG (NLR-PEG) showed higher intracellular retention amount than the short-rod FMSN-PEG (NSR-PEG) and the sphere FMSN-PEG (NS-PEG) almost over 8 h. The NSR-PEG showed the lowest intracellular amount especially with prolonged incubation time. We also found that the cellular entry pathway of NS-PEG, NSR-PEG, and NLR-PEG into Hela cells was regulated by particle shape. Spherical particles preferred to be internalized via the clathrin-mediated pathway, whereas MSN with larger aspect ratios (ARs) favored to be internalized via caveolae-mediated pathway, which could explain their different uptake kinetics. Our findings may provide uful information for optimizing the nano-bad drug delivery and bio-imaging systems.
Keywords:PEGylation, shape, rum protein, mesoporous silica nanoparticle, endocytotic mechanism
1. Introduction
Mesoporous silica nanoparticles (MSN) with rigid structure, high specific surface area, large pore volume, tunable pore structure, great surface-modification capability and good biocompatibility have attracted great attentions for potential biomedical and biotechnological applications, such as protein/
drug/gene delivery [1-3], cancer targeting therapy [4], and bio-imaging [5]. Particularly, previous studies including our own [6-9] have shown that MSN
can be efficiently endocytod and trafficked in mammalian cells. It is well known that cellular uptake and subquent intracellular processing determine the final efficiency of guest molecules delivery by nanocarriers. Current evidences support that the nanoparticles could enter cells by means of endocytosis. It is distinguished that the different endocytotic pathways, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis, might affect the kinetics of intracellular complex processing and the final fate of nanoparticles with loaded guest molecules. For a sharpened understanding about intracellular fates of nanocarriers and efficiently delivering encapsulated guest molecules into given cells, the cellular uptake kinetics, the intracellular trafficking and the uptake mechanism, should be paid due considerations [10].
To date, it has be revealed that the uptake behaviors could be governed by cell types [11,12] and different chemophysical properties of nanoparticles, such as size [13,14], surface chemistry [15,16], and particle composition [17,18]. Recently, particle shape, which is an important physicochemical property of nanoparticles, has been gained great attention and demonstrated experimentally and theoretically to exert a great effect on cellular uptake behaviors[19-21]. Several studies have tried to
explore the specific roles of particle shape on in vitro and in vivo biological behaviors of MSN. For example, Yu et al.[14] revealed that MSN with AR of 2 possd higher hemolytic activity than that with AR of 1, 4, and 8, but the cellular toxicity on RAW 264.7 cells and A549 cells was not governed by particle shape. Our previous study showed that MSN with larger AR had a greater impact on cell proliferation, apoptosis, cytoskeleton formation, adhesion and migration, and the cellular uptake rates of MSN with
larger AR were faster than that of MSN with short AR at the 0.5 h time point [8]. We also found that the in vivo biodistribution, clearance, and biocompatibility of MSN were regulated by particle shape. Short-rod MSN (AR=1.5) was easily trapped in the liver and had a more rapid clearance rate than long-rod MSN (AR=5) in the excretion routes of urine and feces [22]. However, to the best of our knowledge, the shape effects of MSN on cellular uptake kinetics and endocytosis mechanism have still received little attention [16, 21].
室字组词
Recently, Meng et al. [23] showed that MSN with an AR of 2.1~2.5 were uptaken in higher quantities compared to shorter or longer length rods, and MSN with an AR of around 2 were internalized by macropinocytosis. However, the possible difference in uptake pathway of different shaped MSN was not been considered. Trewyn et al. [17] found that cellular uptake kinetics of spherical and tube-shap
ed FITC-doped MSN by CHO and fibroblast cells were regulated by particle shape and cell types. However, the possible reasons of different uptake kinetics induced by particle shape were not discusd. In addition, the stability of MSN in cellular incubation media was not considered. It has been reported that the components of incubation media, especially rum proteins, play significant roles in regulating dispersion status of nanoparticles and their interactions with cells [12,24]. The dispersity of nanoparticles also influences the fluorescent stability, which should be paid enough consideration to ensure the final accurate readout. Thus, a more controllable and stable system should be developed to explore the effect of shape on cellular uptake kinetics and mechanism. Polyethylene glycol (PEG), approved by FDA, has been widely ud as a surface modifying agent to increa the dispersity of nanoparticles and can greatly increa the circulation half-life by inhibition of
