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Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Chen F, Zhang XH, Hu XD, Zhang W, Lou ZC, Xie LH, Liu PD, Zhang HQ - Int J Nanomedicine (2015)

Bottom Line: NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death.However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials.These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

View Article: PubMed Central - PubMed

Affiliation: College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.

ABSTRACT
Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

No MeSH data available.


Related in: MedlinePlus

Detection of ROS in MCF-7 cells by flow cytometry.Notes: (A) Suppression of ROS generation in MCF-7 cells by NGA-CNPs. Cells were treated with indicated concentrations of NGA-CNPs without (top) or with (bottom) subsequent radiation treatment. A fluorometric assay based on the oxidation of DCFH-DA by intracellular oxidants was used in conjunction with flow cytometry to detect ROS. (B) Ce 3d3/2, 5/2 XPS spectrum for NGA-CNPs.Abbreviations: ROS, reactive oxygen species; NGA-CNP, ceria nanoparticle modified with neogambogic acid; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; XPS, X-ray photoelectron spectroscopy.
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f9-ijn-10-4957: Detection of ROS in MCF-7 cells by flow cytometry.Notes: (A) Suppression of ROS generation in MCF-7 cells by NGA-CNPs. Cells were treated with indicated concentrations of NGA-CNPs without (top) or with (bottom) subsequent radiation treatment. A fluorometric assay based on the oxidation of DCFH-DA by intracellular oxidants was used in conjunction with flow cytometry to detect ROS. (B) Ce 3d3/2, 5/2 XPS spectrum for NGA-CNPs.Abbreviations: ROS, reactive oxygen species; NGA-CNP, ceria nanoparticle modified with neogambogic acid; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; XPS, X-ray photoelectron spectroscopy.

Mentions: NGA-CNP treatment inhibited endogenous and radiation-induced ROS formation (Figure 9A), in contrast with the reported effects of other nanomaterials.36 This may be explained by the oxygen vacancy sites on the surface of the nanoceria lattice,54 which have cerium (3+) atoms at the center surrounded by cerium (4+) atoms that can absorb ROS.55 Ce 3D features collected for reference powders (NGA-CNPs) were investigated in order to determine the positions of various components and were deconvoluted using a peak-fitting process. The NGA-CNP spectrum was composed of two multiplets (u and v) corresponding to the spin–orbit split 3d3/2 and 3d3/5 core boles shown in Figure 9B.56 The spin–orbit splitting was approximately 18.6 eV, and the intensity ratio I(3d5/2)/I(3d3/2) was fixed at 1.5.57 The highest binding energy peaks, u″′ and v″′ were located at around 916.9 eV and 898.3 eV, respectively, while the satellite peaks u″′ and v″′ associated with Ce 3d3/2 indicated the presence of Ce4+ and Ce3+, respectively, in NGA-CNPs. The lowest binding energy states u, u″, v, and v″ located at 901.3 eV, 907.3 eV, 882.7 eV, and 888.5±0.1 eV, respectively, were the result of Ce 3d94f2 O 2p4 and Ce 3d94f1 O 2p5 final states.58,59 These findings suggest that the NGA-CNP-induced sensitization of cancer cells to the effects of radiation is not achieved via the generation of ROS.


Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Chen F, Zhang XH, Hu XD, Zhang W, Lou ZC, Xie LH, Liu PD, Zhang HQ - Int J Nanomedicine (2015)

Detection of ROS in MCF-7 cells by flow cytometry.Notes: (A) Suppression of ROS generation in MCF-7 cells by NGA-CNPs. Cells were treated with indicated concentrations of NGA-CNPs without (top) or with (bottom) subsequent radiation treatment. A fluorometric assay based on the oxidation of DCFH-DA by intracellular oxidants was used in conjunction with flow cytometry to detect ROS. (B) Ce 3d3/2, 5/2 XPS spectrum for NGA-CNPs.Abbreviations: ROS, reactive oxygen species; NGA-CNP, ceria nanoparticle modified with neogambogic acid; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; XPS, X-ray photoelectron spectroscopy.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542556&req=5

f9-ijn-10-4957: Detection of ROS in MCF-7 cells by flow cytometry.Notes: (A) Suppression of ROS generation in MCF-7 cells by NGA-CNPs. Cells were treated with indicated concentrations of NGA-CNPs without (top) or with (bottom) subsequent radiation treatment. A fluorometric assay based on the oxidation of DCFH-DA by intracellular oxidants was used in conjunction with flow cytometry to detect ROS. (B) Ce 3d3/2, 5/2 XPS spectrum for NGA-CNPs.Abbreviations: ROS, reactive oxygen species; NGA-CNP, ceria nanoparticle modified with neogambogic acid; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; XPS, X-ray photoelectron spectroscopy.
Mentions: NGA-CNP treatment inhibited endogenous and radiation-induced ROS formation (Figure 9A), in contrast with the reported effects of other nanomaterials.36 This may be explained by the oxygen vacancy sites on the surface of the nanoceria lattice,54 which have cerium (3+) atoms at the center surrounded by cerium (4+) atoms that can absorb ROS.55 Ce 3D features collected for reference powders (NGA-CNPs) were investigated in order to determine the positions of various components and were deconvoluted using a peak-fitting process. The NGA-CNP spectrum was composed of two multiplets (u and v) corresponding to the spin–orbit split 3d3/2 and 3d3/5 core boles shown in Figure 9B.56 The spin–orbit splitting was approximately 18.6 eV, and the intensity ratio I(3d5/2)/I(3d3/2) was fixed at 1.5.57 The highest binding energy peaks, u″′ and v″′ were located at around 916.9 eV and 898.3 eV, respectively, while the satellite peaks u″′ and v″′ associated with Ce 3d3/2 indicated the presence of Ce4+ and Ce3+, respectively, in NGA-CNPs. The lowest binding energy states u, u″, v, and v″ located at 901.3 eV, 907.3 eV, 882.7 eV, and 888.5±0.1 eV, respectively, were the result of Ce 3d94f2 O 2p4 and Ce 3d94f1 O 2p5 final states.58,59 These findings suggest that the NGA-CNP-induced sensitization of cancer cells to the effects of radiation is not achieved via the generation of ROS.

Bottom Line: NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death.However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials.These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

View Article: PubMed Central - PubMed

Affiliation: College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.

ABSTRACT
Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

No MeSH data available.


Related in: MedlinePlus