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

Prylutska, Svitlana; Grynyuk, І. І.; Skaterna, T. D.; Horak, I. R.; Grebinyk, Anna; Дробот, Л. Б.; Matyshevska, Olga; Senenko, A.; Prylutskyy, Yuriy; Наумовец, А.Г.; Ritter, Uwe; Frohme, Marcus

doi:10.1007/s00204-019-02441-6

Cited by 32 publications

(8 citation statements)

References 51 publications

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“…In a pioneering attempt, Evstigneev et al [57] showed a simple and fast method of noncovalent C 60 complexation with Doxorubicin in water and later in a physiological solution [59]. The strategy was applied for C 60 complexation with other chemotherapeutic drugs including Cisplatin and Landomycin A. Molecular modeling, spectroscopy, atomic-force microscopy, mass spectrometry, dynamic light, and small-angle X-ray/neutron scattering evidenced nanocomplex formation [54,56,59,60,80]. The proposed nanosystems were shown to have a higher toxicity compared with the free drugs in vitro and in vivo [54].…”

Section: Discussionmentioning

confidence: 99%

C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

et al. 2019

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A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV–Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C60 binding in an aqueous solution. Complexation with C60 was found to promote Ber intracellular uptake. By increasing C60 concentration, the C60-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C60-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C60 improved its in vitro efficiency against cancer cells.

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Section: Discussionmentioning

confidence: 99%

C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

et al. 2019

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“…In our previous studies, it was shown that when Dox or Cis, which are the golden standards of anticancer medicines, were immobilized on C 60 , their intracellular concentration in cancer cells was increased, leading to higher toxicity and a more pronounced antitumor effect compared with the free drug against various human tumor cell lines in vitro [22,23,49,50] and metastatic mice LLC in vivo [51,52]. This work shows that Ber, immobilized on C 60 , almost completely blocks metastasis in mice.…”

Section: Discussionmentioning

confidence: 76%

“…We have previously demonstrated that C 60 could be a favorable nanoplatform for targeted delivery of chemotherapeutic drugs and optimization of their efficiency against cancer cells. We have developed a quick and simple strategy for the non-covalent complexation of Doxorubicin (Dox), Cisplatin (Cis), and Ber with C 60 and confirmed its efficiency for the substantial potentiation of drugs intracellular uptake and their cytotoxic effects in the range of low doses against leukemic and lung cancer cell lines [22][23][24].…”

Section: Introductionmentioning

confidence: 91%

Nanocomplex of Berberine with C60 Fullerene Is a Potent Suppressor of Lewis Lung Carcinoma Cells Invasion In Vitro and Metastatic Activity In Vivo

et al. 2021

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Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber’ low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C60 fullerene (C60). The complexation between C60 and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C60-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C60 demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C60-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C60 can be used as an additional therapeutic strategy against aggressive lung cancer.

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“…C 60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells [ 99 ]. C 60 fullerene, as a component of the C 60 –Cis-Pt nanocomplex has been reported to increase the Cis-Pt entry and an intracellular accumulation thus, contributing to the drug’s toxic effect [ 17 ]. Fullerenol/Dox nanocomplexes, with a diameter of 50–80 nm and about 25% drug loading efficiency, significantly reduce the growth of melanoma and LLC cells and induce cell apoptosis in vitro and prohibit B16/F10 tumor growth in vivo [ 71 ].…”

Section: Fullerene Derivatives: Promising New Anti-tumor Nanoparticlesmentioning

confidence: 99%

“…20 cellular immunity activation T lymphocytes and macrophages/C57BL/6 mice improve the immune response to kill tumor cells. [3] tumor metastasis inhibition EMT-6 breast cancer metastasis model inhibit tumor cell proliferation [4] Gd@C 82 (OH) 22 cellular immunity activation dendritic cells and macrophages /C57BL/6 activate Th1 Immune Responses [5,6] angiogenesis suppression malignant human breast cancer models/cancer stem cells reduce tumor microvessels density (MVD) [7][8][9] inhibition of oxidative stress hepatoma cell normalize the activity of enzymes related to oxidative stress [10] cell cycle regulation MCF-7 and ECV304 cell induce the G0/G1 phase arrest [11,12] tumor metastasis inhibition BALB/c nu/nu female mice inhibit MMP-2 and MMP-9 with high antitumoral efficacy [13] C 60 (OH) 24 inhibition of oxidative stress A549 cells attenuate oxidative stress-induced apoptosis [14] Gd@C 82 -(EDA) 8 maintain a reactive oxygen species (ROS) balance human epidermal keratinocytes-adult scavenge hydroxyl radicals [15] β-alanine modified gadofullerene nanoparticles (GFNPs) tumor photodynamic therapy melanoma cancer cells/female BALB/c nude mice disrupt tumor vasculatures [16] C 60 -Cisplatin nanocomplexs drug delivery carriers lewis lung carcinoma cells enhance the toxic effect of cisplatin on lung cancer cells [17] C 60 -Berberiner nanocomplexes CCRF-CEM cells inhibit the proliferation of CCRF-CEM cells [18] Fullerenes can be modified by carbon cage internal nesting and carbon cage surface modification. On the one hand, the hollow interior of the carbon cage can contain single atoms, clusters of atoms and even small molecules [19,20].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Activity and Potential Mechanism of Novel Fullerene Derivative Nanoparticles

Kollie

Liu

et al. 2021

Molecules

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The development of novel nanoparticles as a new generation therapeutic drug platform is an active field of chemistry and cancer research. In recent years, fullerene nanoparticles have received extensive attention due to their unique physical and chemical properties. Properly modified fullerene nanoparticles have excellent biocompatibility and significant anti-tumor activity, which makes them have broad application prospects in the field of cancer therapy. Therefore, understanding the anti-tumor mechanism of fullerene nanoparticles is of great significance for the design and development of anti-tumor drugs with low toxicity and high targeting. This review has focused on various anti-tumor mechanisms of fullerene derivatives and discusses their toxicity and their distribution in organisms. Finally, the review points out some urgent problems that need solution before fullerene derivatives as a new generation of anti-tumor nano-drug platform enter clinical research.

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

Cited by 32 publications

References 51 publications

C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

Nanocomplex of Berberine with C60 Fullerene Is a Potent Suppressor of Lewis Lung Carcinoma Cells Invasion In Vitro and Metastatic Activity In Vivo

Antitumor Activity and Potential Mechanism of Novel Fullerene Derivative Nanoparticles

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