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Alkyl-capped silicon nanocrystals lack cytotoxicity and have enhanced intracellular accumulation in malignant cells via cholesterol-dependent endocytosis.

Alsharif NH, Berger CE, Varanasi SS, Chao Y, Horrocks BR, Datta HK - Small (2009)

Bottom Line: The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D.The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol.The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non-malignant cells therefore offers potential application in the management of human neoplastic conditions.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine Newcastle University, Framlington Place Newcastle upon Tyne, UK.

ABSTRACT
Nanocrystals of various inorganic materials are being considered for application in the life sciences as fluorescent labels and for such therapeutic applications as drug delivery or targeted cell destruction. The potential applications of the nanoparticles are critically compromised due to the well-documented toxicity and lack of understanding about the mechanisms involved in the intracellular internalization. Here intracellular internalization and toxicity of alkyl-capped silicon nanocrystals in human neoplastic and normal primary cells is reported. The capped nanocrystals lack cytotoxicity, and there is a marked difference in the rate and extent of intracellular accumulation of the nanoparticles between human cancerous and non-cancerous primary cells, the rate and extent being higher in the malignant cells compared to normal human primary cells. The exposure of the cells to the alkyl-capped nanocrystals demonstrates no evidence of in vitro cytotoxicity when assessed by cell morphology, apoptosis, and cell viability assays. The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D. The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol. The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non-malignant cells therefore offers potential application in the management of human neoplastic conditions.

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Schematic molecular model of the SiNCs used in this work. The luminescent silicon core is crystalline with similar lattice parameters to the bulk. The diameter of the core is about 2.5 nm and the diameter of the whole particle including the undecyl capping layer is about 5 nm.
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fig01: Schematic molecular model of the SiNCs used in this work. The luminescent silicon core is crystalline with similar lattice parameters to the bulk. The diameter of the core is about 2.5 nm and the diameter of the whole particle including the undecyl capping layer is about 5 nm.

Mentions: The NCs comprise a crystalline silicon core covered by a C11 alkyl monolayer (Figure 1). The silicon core is 2.5 nm in diameter and the size of the whole particle, including the alkyl monolayer, is about 5 nm (detailed characterization is provided in References 18,20,21). The NCs are intensely luminescent under excitation with λex < 550 nm and the emission spectrum is independent of the excitation wavelength.21 The NCs are highly hydrophobic and therefore have negligible miscibility in water. They are very soluble in nonpolar solvents, and solutions thereof can be mixed with excess water to form a lyophobic sol that is stable against flocculation for periods up to several months.20 A range of solvents were used, including tetrahydrofuran (THF), toluene, dimethylsulfoxide (DMSO), and diethyl ether (ether). The NCs were found to be most readily soluble in THF, toluene, and ether.


Alkyl-capped silicon nanocrystals lack cytotoxicity and have enhanced intracellular accumulation in malignant cells via cholesterol-dependent endocytosis.

Alsharif NH, Berger CE, Varanasi SS, Chao Y, Horrocks BR, Datta HK - Small (2009)

Schematic molecular model of the SiNCs used in this work. The luminescent silicon core is crystalline with similar lattice parameters to the bulk. The diameter of the core is about 2.5 nm and the diameter of the whole particle including the undecyl capping layer is about 5 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2962801&req=5

fig01: Schematic molecular model of the SiNCs used in this work. The luminescent silicon core is crystalline with similar lattice parameters to the bulk. The diameter of the core is about 2.5 nm and the diameter of the whole particle including the undecyl capping layer is about 5 nm.
Mentions: The NCs comprise a crystalline silicon core covered by a C11 alkyl monolayer (Figure 1). The silicon core is 2.5 nm in diameter and the size of the whole particle, including the alkyl monolayer, is about 5 nm (detailed characterization is provided in References 18,20,21). The NCs are intensely luminescent under excitation with λex < 550 nm and the emission spectrum is independent of the excitation wavelength.21 The NCs are highly hydrophobic and therefore have negligible miscibility in water. They are very soluble in nonpolar solvents, and solutions thereof can be mixed with excess water to form a lyophobic sol that is stable against flocculation for periods up to several months.20 A range of solvents were used, including tetrahydrofuran (THF), toluene, dimethylsulfoxide (DMSO), and diethyl ether (ether). The NCs were found to be most readily soluble in THF, toluene, and ether.

Bottom Line: The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D.The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol.The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non-malignant cells therefore offers potential application in the management of human neoplastic conditions.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine Newcastle University, Framlington Place Newcastle upon Tyne, UK.

ABSTRACT
Nanocrystals of various inorganic materials are being considered for application in the life sciences as fluorescent labels and for such therapeutic applications as drug delivery or targeted cell destruction. The potential applications of the nanoparticles are critically compromised due to the well-documented toxicity and lack of understanding about the mechanisms involved in the intracellular internalization. Here intracellular internalization and toxicity of alkyl-capped silicon nanocrystals in human neoplastic and normal primary cells is reported. The capped nanocrystals lack cytotoxicity, and there is a marked difference in the rate and extent of intracellular accumulation of the nanoparticles between human cancerous and non-cancerous primary cells, the rate and extent being higher in the malignant cells compared to normal human primary cells. The exposure of the cells to the alkyl-capped nanocrystals demonstrates no evidence of in vitro cytotoxicity when assessed by cell morphology, apoptosis, and cell viability assays. The internalization of the nanocrystals by Hela and SW1353 cells is almost completely blocked by the pinocytosis inhibitors filipin, cytochalasin B, and actinomycin D. The internalization process is not associated with any surface change in the nanoparticles, as their luminescence spectrum is unaltered upon transport into the cytosol. The observed dramatic difference in the rate and extent of internalization of the nanocrystals between malignant and non-malignant cells therefore offers potential application in the management of human neoplastic conditions.

Show MeSH
Related in: MedlinePlus