Toxicity of C60 fullerene–cisplatin nanocomplex against Lewis lung carcinoma cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04-15

AUTHORS

Svitlana Prylutska, Iryna Grynyuk, Tetiana Skaterna, Iryna Horak, Anna Grebinyk, Liudmyla Drobot, Olga Matyshevska, Anton Senenko, Yuriy Prylutskyy, Anton Naumovets, Uwe Ritter, Marcus Frohme

ABSTRACT

Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C60 fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Scanning tunneling microscopy showed that the minimum size of C60–Cis-Pt nanoparticles in aqueous colloid solution was 1.1 nm whereas that of C60 fullerene was 0.72 nm, thus confirming formation of the nanocomplex. The cytotoxic effect of C60–Cis-Pt nanocomplex against LLC cells was shown to be higher with IC50 values 3.3 and 4.5 times lower at 48 h and 72 h, respectively, as compared to the free drug. 12.5 µM Cis-Pt had no effect on LLC cell viability and morphology while C60–Cis-Pt nanocomplex in Cis-Pt-equivalent concentration substantially decreased the cell viability, impaired their shape and adhesion, inhibited migration and induced accumulation in proapoptotic subG1 phase. Apoptosis induced by the C60–Cis-Pt nanocomplex was confirmed by caspase 3/7 activation and externalization of phosphatidylserine on the outer surface of LLC cells with the double Annexin V-FITC/PI staining. We assume that C60 fullerene as a component of the C60–Cis-Pt nanocomplex promoted Cis-Pt entry and intracellular accumulation thus contributing to intensification of the drug’s toxic effect against lung cancer cells. More... »

PAGES

1213-1226

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00204-019-02441-6

DOI

http://dx.doi.org/10.1007/s00204-019-02441-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113475744

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30989314


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30 schema:description Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C60 fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Scanning tunneling microscopy showed that the minimum size of C60–Cis-Pt nanoparticles in aqueous colloid solution was 1.1 nm whereas that of C60 fullerene was 0.72 nm, thus confirming formation of the nanocomplex. The cytotoxic effect of C60–Cis-Pt nanocomplex against LLC cells was shown to be higher with IC50 values 3.3 and 4.5 times lower at 48 h and 72 h, respectively, as compared to the free drug. 12.5 µM Cis-Pt had no effect on LLC cell viability and morphology while C60–Cis-Pt nanocomplex in Cis-Pt-equivalent concentration substantially decreased the cell viability, impaired their shape and adhesion, inhibited migration and induced accumulation in proapoptotic subG1 phase. Apoptosis induced by the C60–Cis-Pt nanocomplex was confirmed by caspase 3/7 activation and externalization of phosphatidylserine on the outer surface of LLC cells with the double Annexin V-FITC/PI staining. We assume that C60 fullerene as a component of the C60–Cis-Pt nanocomplex promoted Cis-Pt entry and intracellular accumulation thus contributing to intensification of the drug’s toxic effect against lung cancer cells.
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37 C60
38 C60 fullerene
39 LLC cell viability
40 LLC cells
41 Lewis lung carcinoma cells
42 PI staining
43 Pt nanoparticles
44 V-FITC/PI staining
45 accumulation
46 activation
47 adhesion
48 agents
49 aim
50 apoptosis
51 aqueous colloid solution
52 cancer cells
53 carcinoma cells
54 caspase-3/7 activation
55 cell viability
56 cells
57 cis-Pt
58 cisplatin
59 colloid solution
60 comparison
61 components
62 concentration
63 conjugation
64 cytotoxic agents
65 cytotoxic effects
66 drug targeting
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68 drugs
69 effect
70 efficiency
71 entry
72 equivalent concentrations
73 externalization
74 externalization of phosphatidylserine
75 formation
76 free drug
77 fullerenes
78 high toxicity
79 induced accumulation
80 intensification
81 interaction
82 intracellular accumulation
83 lung cancer cells
84 lung carcinoma cells
85 microscopy
86 migration
87 minimum size
88 morphology
89 nanocarriers
90 nanocomplexes
91 nanoparticles
92 non-selective effects
93 noncovalent interactions
94 options
95 origin
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97 phase
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