Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 13, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12951-015-0068-6
Keywords
Mesoporous silica nanoparticles; Lactose; Asialoglycoprotein receptor; Docetaxel
Funding
- National Natural Science Foundation of China [81173002]
- National Science and Technology Pillar Program [2012BAI35B02]
- International Cooperation and Exchanges Program of China [2008DFA31080]
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Background: Mesoporous silica nanoparticles (MSNs) have several attractive properties as a drug delivery system, such as ordered porous structure, large surface area, controllable particle size as well as interior and exterior dual-functional surfaces. The purpose of this study was to develop novel lactosaminated mesoporoussilica nanoparticles (Lac-MSNs) for asialoglycoprotein receptor (ASGPR) targeted anticancer drug delivery. Results: Lac-MSNs with an average diameter of approximately 100 nm were prepared by conjugation of lactose with 3-aminopropyl triethoxysilane modified MSNs. Characterization of Lac-MSNs indicated a huge Brunauer-Emmett-Teller (BET) surface area (1012 m(2)/g), highly ordered 2D hexagonal symmetry, an unique mesoporous structure with average pore size of 3.7 nm. The confocal microscopy and flow cytometric analysis illustrated Lac-MSNs were effectively endocytosed by ASGPR-positive hepatoma cell lines, HepG2 and SMMC7721. In contrast, non-selective endocytosis of Lac-MSNs was found in ASGPR-negative NIH 3T3 cells. The cellular uptake study showed the internalization process was energy-consuming and predominated by clathrin-mediated pathway. Model drug docetaxel (DTX) was loaded in the mesopores of Lac-MSNs by wetness impregnation method. In vitro cytotoxicity assay showed that DTX transported by Lac-MSNs effectively inhibited the growth of HepG2 and SMMC7721 cells in a time- and concentration- dependent manner. Conclusions: These results demonstrated that Lac-MSNs could be a promising inorganic carrier system for targeted intracellular anti-cancer drug delivery.
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