Online citations, reference lists, and bibliographies.
← Back to Search

Genotoxicity Evaluation Of Stearic Acid Grafted Chitosan Oligosaccharide Nanomicelles.

Peng Hu, T. Wang, Q. Xu, Y. Chang, Honggang Tu, Y. Zheng, J. Zhang, Yuying Xu, J. Yang, H. Yuan, Fuqiang Hu, Xinqiang Zhu
Published 2013 · Chemistry, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Stearic acid grafted chitosan oligosaccharide (CSO-SA) nanomicelles could be promptly internalized into cancer cells; therefore, it is regarded as a promising drug carrier for cancer therapy. However, the toxicity of CSO-SA is not clear. In the present study, the genotoxic effects of CSO-SA nanomicelles (with high substitution degree of SA, 42.6±3.8%) were evaluated with a battery of genotoxicity assays. Mutagenicity was not found in Ames Salmonella/microsome mutagenicity assay (Ames test), while mild but definite positive results were observed in mouse bone marrow micronucleus assay and single cell gel electrophoresis (SCGE or comet assay) in A549 cells. CSO-SA was also found to induce apoptosis and oxidative stress through the induction of reactive oxygen species (ROS) in a dose-dependent manner in A549 cells. Preincubation with the free radical scavenger N-acetyl-l-cysteine (NAC) decreased the intracellular ROS level and alleviated the DNA damage in A549 cells. Expression levels of cleaved poly ADP-ribose polymerase (PARP), caspase-9 and caspase-3, markers of apoptosis, were significantly higher in CSO-SA treated cells. In conclusion, these results suggested significant genotoxicity of high doses of CSO-SA nanomicelles in vivo and in vitro. Oxidative stress was, at least partially, the possible mechanism underlying the genotoxicity induced by CSO-SA.
This paper references
10.1016/j.ijpharm.2010.02.017
Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: factors affecting the complexation.
Yong-Zhong Du (2010)
10.1016/S1383-5718(97)00126-5
The photogenotoxicity of titanium dioxide particles.
Y. Nakagawa (1997)
10.1186/1477-3155-2-3
Applications of nanoparticles in biology and medicine
OV Salata (2004)
10.1016/S0027-5107(00)00064-6
The Ames Salmonella/microsome mutagenicity assay.
K. Mortelmans (2000)
In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human hepg 2 hepatoma cells
Xun Lu (2011)
10.1016/S0144-8617(00)00326-X
Optimum dose of chitin and chitosan for organization of non-woven fabric in the subcutaneous tissue
K. Kojima (2001)
10.1016/S0891-5849(99)00107-0
Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader.
Hongshun Wang (1999)
10.1186/1743-8977-7-1
SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells
X. Yang (2009)
10.1016/j.toxlet.2011.11.004
Evaluation of cytotoxic, genotoxic and inflammatory responses of micro- and nano-particles of granite on human lung fibroblast cell IMR-90.
I. Ahmad (2012)
10.1016/S0928-0987(99)00032-9
Chitosans as absorption enhancers of poorly absorbable drugs. 3: Influence of mucus on absorption enhancement.
N. G. Schipper (1999)
Torchilin , Micelles from lipid derivatives of water - soluble polymers as delivery systems for poorly soluble drugs , Adv
A. N. Lukyanov (2004)
10.1038/cddis.2011.27
A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
H-L Liu (2011)
10.4014/JMB.0811.603
Suppression of metastasis of human breast cancer cells by chitosan oligosaccharides.
Kyung-Soo Nam (2009)
10.1074/jbc.M413344200
Novel Role for Amphiregulin in Protection from Liver Injury*
C. Berasain (2005)
10.1016/j.taap.2009.10.016
Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster.
M. Ahamed (2010)
10.1039/B506241A
Practical control of SERRS enhancement.
D. Cunningham (2006)
10.1016/j.mrrev.2008.10.002
Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations--many questions, some answers.
R. Landsiedel (2009)
10.1007/S11051-011-0586-6
In vitro evaluation of cytotoxic and inflammatory properties of silica nanoparticles of different sizes in murine RAW 264.7 macrophages
M. Park (2011)
10.1016/j.biomaterials.2010.04.014
Autophagy and oxidative stress associated with gold nanoparticles.
J. J. Li (2010)
10.1016/0165-1161(83)90010-9
Revised methods for the Salmonella mutagenicity test.
D. Maron (1983)
10.1016/j.biomaterials.2009.04.009
NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials.
N. Singh (2009)
10.1163/156856205774472281
Sustained release of PEG-g-chitosan complexed DNA from poly(lactide-co-glycolide)
Y. H. Yun (2005)
10.2147/IJN.S24005
In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells
X. Lu (2011)
10.1016/0165-1161(75)90046-1
Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test.
B. Ames (1975)
10.1001/JAMA.287.9.1132
Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution.
C. Pope (2002)
10.1016/s0168-3659(97)00136-3
Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosanâEDTA conjugates
A. Bernkop-Schnürch (1998)
10.1016/j.tiv.2011.02.015
Toxic response of nickel nanoparticles in human lung epithelial A549 cells.
M. Ahamed (2011)
10.3109/1061186X.2010.499465
Improved cytotoxicity and multidrug resistance reversal of chitosan based polymeric micelles encapsulating oxaliplatin
Y. Xu (2011)
10.1016/j.tox.2011.02.010
Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.
M. Ahamed (2011)
10.1016/J.MRGENTOX.2006.04.015
Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: Genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells.
E. K. Dufour (2006)
10.2174/1389201033489748
Application of chitin and chitosan derivatives in the pharmaceutical field.
Y. Kato (2003)
10.1016/j.brainres.2006.11.037
Caspase-dependent apoptosis induced by calcineurin inhibitors was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical cells
T. Takadera (2007)
10.1080/15287390701601251
Single-walled Carbon Nanotubes: Geno- and Cytotoxic Effects in Lung Fibroblast V79 Cells
E. Kisin (2007)
Single - walled carbon nanotubes : genoand cytotoxic effects in lung fibroblast V 79 cells
A. R. Murray (2007)
10.1016/S0006-2952(03)00083-2
Evaluation of the probes 2',7'-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation.
O. Myhre (2003)
10.1016/J.CANLET.2007.01.008
Induction of mitochondria-dependent apoptosis through the inhibition of mevalonate pathway in human breast cancer cells by YM529, a new third generation bisphosphonate.
H. Nakajima (2007)
10.1056/NEJM200104193441614
Fine particulate air pollution and mortality in 20 U.S. cities.
J. Sarnat (2001)
10.1016/j.ejps.2011.09.004
Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability.
A. Dube (2011)
10.1088/0957-4484/18/49/495101
High cytotoxicity and resistant-cell reversal of novel paclitaxel loaded micelles by enhancing the molecular-target delivery of the drug.
Jian You (2007)
10.3390/md8071962
Chitosan Modification and Pharmaceutical/Biomedical Applications
J. Zhang (2010)
10.2131/jts.32.575
Mutagenicity of water-soluble FePt nanoparticles in Ames test.
S. Maenosono (2007)
10.1093/jmcb/mjp002
PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway.
C. Li (2009)
10.1002/(SICI)1097-0320(19960601)24:2<131::AID-CYTO5>3.0.CO;2-M
A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture.
M. van Engeland (1996)
Car - riere , In vitro evaluation of SiC nanoparticles impact on A 549 pulmonary cells : cyto, genotoxicity and oxidative stress
M. L. Jugan S. Barillet (2010)
10.1158/0008-5472.CAN-09-2496
Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice.
Bénédicte Trouiller (2009)
10.1016/j.cell.2008.10.044
Identification of a Molecular Signaling Network that Regulates a Cellular Necrotic Cell Death Pathway
J. Hitomi (2008)
10.1016/j.fct.2011.04.036
Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats.
S. P. Yoon (2011)
10.1186/1743-8977-7-22
Nanomaterial cytotoxicity is composition, size, and cell type dependent
S. Sohaebuddin (2009)
10.1080/08958370490439597
Translocation of Inhaled Ultrafine Particles to the Brain
G. Oberdörster (2004)
10.1016/0014-4827(88)90265-0
A simple technique for quantitation of low levels of DNA damage in individual cells.
N. Singh (1988)
10.1007/s00204-010-0545-5
Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549
Rasmus Foldbjerg (2010)
Protec - tive effects of chitosan oligosaccharide on paraquatinduced nephrotoxicity in rats
M. S. Han (2011)
10.1007/s13273-010-0045-y
Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by silica nanomaterials in human neuronal cell line
Youn-Jung Kim (2010)
10.2131/JTS.34.119
Mutagenicity of water-soluble ZnO nanoparticles in Ames test.
R. Yoshida (2009)
Novel self-aggregates of chitosan oligosaccharide grafted stearic acid: preparation, characterization and protein association.
F. Hu (2006)
10.1016/j.toxlet.2010.03.1126
SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells
X. Yang (2010)
10.1002/ADMA.200701853
GOLD NANOPARTICLES INDUCE OXIDATIVE DAMAGE IN LUNG FIBROBLASTS IN VITRO
J. J. Li (2008)
10.1016/J.IJPHARM.2006.02.026
A novel chitosan oligosaccharide-stearic acid micelles for gene delivery: properties and in vitro transfection studies.
F. Hu (2006)
10.1016/j.toxlet.2010.07.009
In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress.
S. Barillet (2010)
10.1016/J.TOXLET.2007.04.008
Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management.
D. Warheit (2007)
10.1016/J.ADDR.2003.12.004
Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.
A. Lukyanov (2004)
10.1016/j.mrgentox.2011.01.014
Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro.
Yuanyuan Guo (2011)
10.1016/j.bbrc.2010.05.091
Nitroalkenes induce rat aortic smooth muscle cell apoptosis via activation of caspase-dependent pathways.
X. Tang (2010)
10.1016/S0378-5173(98)00378-0
Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA.
S. Richardson (1999)
10.1002/pmic.200800571
Plasma proteome analysis for anti‐obesity and anti‐diabetic potentials of chitosan oligosaccharides in ob/ob mice
S. G. Kumar (2009)



This paper is referenced by
10.1081/E-EBPP-120050068
Chitosan Oligosaccharides: Drug and Gene Delivery
Gaurav Kapadnis (2015)
10.5772/61013
Progress in Genotoxicity Evaluation of Engineered Nanomaterials
X. Guo (2015)
Anticancer activities of oxidant-redox drug combinations in lipid excipients
M. Haigh (2018)
10.1080/00087114.2013.852342
Cytogenetic effects of chitosan-capped silver nanoparticles in the Allium cepa test
D. S. Pesnya (2013)
10.1016/j.bbagen.2014.01.016
Synthesis and characterization of curcumin loaded polymer/lipid based nanoparticles and evaluation of their antitumor effects on MCF-7 cells.
Sathish Sundar Dhilip Kumar (2014)
10.1208/s12249-016-0563-6
Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation
N. Thotakura (2016)
10.1590/1807-3107bor-2018.vol32.0119
Assessment of toxicity and oxidative DNA damage of sodium hypochlorite, chitosan and propolis on fibroblast cells.
Z. Uğur Aydın (2018)
10.24275/uam/izt/dcbi/revmexingquim/2018v17n3/Hernandez
PARTÍCULAS DE QUITOSANO/CARRAGENINA/LISOZIMA: SÍNTESIS, CARACTERIZACIÓN Y ACTIVIDAD ANTIFÚNGICA CONTRA Aspergillus parasiticus
Cynthia Nazareth Hernández-Téllez (2018)
10.1007/s11356-020-10716-0
Phytotoxicity, cytotoxicity, and in vivo antifungal efficacy of chitosan nanobiocomposites on prokaryotic and eukaryotic cells
Alma Carolina Gálvez-Iriqui (2020)
10.2174/1566524019666190917144127
Effects of stearic acid on proliferation, differentiation, apoptosis, and autophagy in porcine intestinal epithelial cells.
Y. Yang (2019)
10.5505/YEDITEPE.2019.96268
Effect of various irrigation solutions on cytokine expression of human gingival fibroblast: in vitro study
Zeliha Uğur Aydın (2019)
10.1093/toxsci/kfy100
Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods
R. Elespuru (2018)
10.1016/B978-0-323-32889-0.00016-9
Role of Nanogenotoxicology Studies in Safety Evaluation of Nanomaterials
H. Louro (2015)
Semantic Scholar Logo Some data provided by SemanticScholar