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Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells.

Wang Y, Zi XY, Su J, Zhang HX, Zhang XR, Zhu HY, Li JX, Yin M, Yang F, Hu YP - Int J Nanomedicine (2012)

Bottom Line: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects.Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis.CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China.

ABSTRACT
In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.

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Transmission electron images of HeLa cells treated with a solution of CONPs (30 μg/mL) for 4 hours. The arrows indicate the accumulation of the CONPs. (A) The CONPs entered a mitochondrion and broke its outer membrane. CONPs existed in vesicles and in the cytoplasm. (B) The endoplasmic reticulum swelled visibly. A structure similar to an autophagy body phagocytized a group of CONPs. (C) The vesicles containing the CONPs appeared to target the outer membrane of the mitochondrion, and the shape of the mitochondrion had changed. (D) CONPs localized in small vesicles and entered or were entering the mitochondrion. (E and F) CONPs broke the membrane of the mitochondrion and caused structural changes.Abbreviations: CONPs, cuprous oxide nanoparticles; M, mitochondrion; ER, endoplasmic reticulum.
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f8-ijn-7-2641: Transmission electron images of HeLa cells treated with a solution of CONPs (30 μg/mL) for 4 hours. The arrows indicate the accumulation of the CONPs. (A) The CONPs entered a mitochondrion and broke its outer membrane. CONPs existed in vesicles and in the cytoplasm. (B) The endoplasmic reticulum swelled visibly. A structure similar to an autophagy body phagocytized a group of CONPs. (C) The vesicles containing the CONPs appeared to target the outer membrane of the mitochondrion, and the shape of the mitochondrion had changed. (D) CONPs localized in small vesicles and entered or were entering the mitochondrion. (E and F) CONPs broke the membrane of the mitochondrion and caused structural changes.Abbreviations: CONPs, cuprous oxide nanoparticles; M, mitochondrion; ER, endoplasmic reticulum.

Mentions: To determine the mechanism of apoptosis, it is essential to know whether the CONPs crossed the cell membrane. We therefore used TEM to analyze HeLa cells that had been treated with 30 μg/mL CONPs for 3–4 hours. As shown in Figure 8(A), we observed that several CONPs were enclosed in small vesicles within the cells. In addition, numerous CONPs were found in the cytoplasm. The CONPs in the cytoplasm had two possible sources. First, the CONPs may have penetrated the cell membrane without breaking it. Alternatively, the CONPs were taken up by cells in small vesicles, but then they broke the membrane of the vesicles and were released into the cytoplasm. Furthermore, all the images showed that CONPs could not efficiently enter the nucleus, lysosomes, or endoplasmic reticulum. However, the CONPs could cause endoplasmic reticulum tumescence (Figure 8B).


Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells.

Wang Y, Zi XY, Su J, Zhang HX, Zhang XR, Zhu HY, Li JX, Yin M, Yang F, Hu YP - Int J Nanomedicine (2012)

Transmission electron images of HeLa cells treated with a solution of CONPs (30 μg/mL) for 4 hours. The arrows indicate the accumulation of the CONPs. (A) The CONPs entered a mitochondrion and broke its outer membrane. CONPs existed in vesicles and in the cytoplasm. (B) The endoplasmic reticulum swelled visibly. A structure similar to an autophagy body phagocytized a group of CONPs. (C) The vesicles containing the CONPs appeared to target the outer membrane of the mitochondrion, and the shape of the mitochondrion had changed. (D) CONPs localized in small vesicles and entered or were entering the mitochondrion. (E and F) CONPs broke the membrane of the mitochondrion and caused structural changes.Abbreviations: CONPs, cuprous oxide nanoparticles; M, mitochondrion; ER, endoplasmic reticulum.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368515&req=5

f8-ijn-7-2641: Transmission electron images of HeLa cells treated with a solution of CONPs (30 μg/mL) for 4 hours. The arrows indicate the accumulation of the CONPs. (A) The CONPs entered a mitochondrion and broke its outer membrane. CONPs existed in vesicles and in the cytoplasm. (B) The endoplasmic reticulum swelled visibly. A structure similar to an autophagy body phagocytized a group of CONPs. (C) The vesicles containing the CONPs appeared to target the outer membrane of the mitochondrion, and the shape of the mitochondrion had changed. (D) CONPs localized in small vesicles and entered or were entering the mitochondrion. (E and F) CONPs broke the membrane of the mitochondrion and caused structural changes.Abbreviations: CONPs, cuprous oxide nanoparticles; M, mitochondrion; ER, endoplasmic reticulum.
Mentions: To determine the mechanism of apoptosis, it is essential to know whether the CONPs crossed the cell membrane. We therefore used TEM to analyze HeLa cells that had been treated with 30 μg/mL CONPs for 3–4 hours. As shown in Figure 8(A), we observed that several CONPs were enclosed in small vesicles within the cells. In addition, numerous CONPs were found in the cytoplasm. The CONPs in the cytoplasm had two possible sources. First, the CONPs may have penetrated the cell membrane without breaking it. Alternatively, the CONPs were taken up by cells in small vesicles, but then they broke the membrane of the vesicles and were released into the cytoplasm. Furthermore, all the images showed that CONPs could not efficiently enter the nucleus, lysosomes, or endoplasmic reticulum. However, the CONPs could cause endoplasmic reticulum tumescence (Figure 8B).

Bottom Line: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects.Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis.CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China.

ABSTRACT
In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.

Show MeSH
Related in: MedlinePlus