Abstract
Different types of bleomycins are used extensively in cancer therapy. Antibiotics scarcely penetrate through cell membranes, leading to the necessity of using high concentrations of the drug and, therefore, overall body toxicity. To study the penetration of an antibiotic into cells, the fluorescein residue (Flu) was introduced in bleomycin A5 (Blm) to form BlmFlu. It was shown by confocal fluorescent microscopy that BlmFlu in the presence of titanium dioxide nanoparticles (TiO2, 3–5 nm), in contrast to free BlmFlu, efficiently penetrate the cell cytoplasm. After being delivered into cells in the presence of TiO2, Blm appeared to be 7–10 times more efficient than free Blm in the fragmentation of intracellular nucleic acids. The results suggest that nanoparticles are very promising to promote the delivery of antibiotics into cells, which will allow reducing their therapeutic dose.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
M. J. Jaroszeski, V. Dang, C. Pottinger, J. Hickey, R. Gilbert, and R. Heller, “Toxicity of anticancer agents mediated by electroporation in vitro,” Anticancer Drugs 11, 201–208 (2000).
S. Sonoda, K. Tachibana, E. Uchino, T. Yamashita, K. Sakoda, K. H. Sonoda, T. Hisatomi, Y. Izumi, and T. Sakamoto, “Inhibition of melanoma by ultrasound-microbubble-aided drug delivery suggests membrane permeabilization,” Cancer Biol. Ther. 6, 1276–1283 (2007).
A. Gabizon, D. C. Price, J. Huberty, R. S. Bresalier, and D. Papahadjopoulos, “Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies,” Cancer Res. 50, 6371–6378 (1990).
D. Arndt, R. Zeisig, D. Bechtel, and I. Fichtner, “Liposomal bleomycin: increased therapeutic activity and decreased pulmonary toxicity in mice,” Drug Deliv. 8, 1–7 (2001).
Y. C. Ho, K. W. Tai, and Y. C. Chang, “Synergistic effects of verapamil on pingyangmycin-induced cytotoxicity and apoptosis in KB cells,” Oral Diseases 13, 40–44 (2007).
N. Orsolic, “Potentiation of bleomycin lethality in HeLa and V79 cells by bee venom,” Arh. Hig. Rada. Toksikol. 60, 317–326 (2009).
M. Zochowska, A. Paca, G. Schoehn, J. P. Andrieu, J. Chroboczek, B. Dublet, and E. Szolajska, “Adenovirus dodecahedron, as a drug delivery vector,” PLoS ONE 4, e5569 (2009).
K. Cho, X. Wang, S. Nie, Z. G. Chen, and D. M. Shin, “Therapeutic nanoparticles for drug delivery in cancer,” Clin. Cancer Res. 14, 1310–1316 (2008).
S. K. Sohaebuddin, P. T. Thevenot, D. Baker, J. W. Eaton, and L. Tang, “Nanomaterial cytotoxicity is composition, size, and cell type dependent,” Fibre Toxicol. 7, 22 (2010).
G. Oberdörster, E. Oberdörster, and J. Oberdörster, “Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles,” Environ. Health Perspec. 113, 823–829 (2005).
W. G. Kreyling, M. Semmler, F. Erbe, P. Mayer, S. Takenaka, H. Schulz, G. Oberdörster, and A. Ziesenis,, “Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low,” Toxicol. Environ. Health 65, 1513–1530 (2002).
G. Oberdörster, Z. Sharp, V. Atudorei, A. Elder, R. Gelein, A. Lunts, W. Kreyling, and C. Cox,, “Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats,” Toxicol. Environ. Health 65, 1531–1543 (2002).
C. A. Dick, D. M. Brown, K. Donaldson, and V. Stone, “The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types,” Inhal. Toxicol. 15, 39–52 (2003).
Z. R. Ismagilov, L. T. Tsikoza, N. V. Shikina, V. F. Zarytova, V. V. Zinov’ev, and S. N. Zagrebel’nyi, “Synthesis and stabilization of nanosized titanium dioxide,” Usp. Khim. 78, 873–885 (2009).
A. Levina, Z. Ismagilov, M. Repkova, N. Shatskaya, N. Shikina, F. Tusikov, and V. Zarytova, “Nanocomposites consisting of titanium dioxide nanoparticles and oligonucleotides,” Nanosci. Nanotech. 12, 1806–1811 (2012).
M. Herrmann, H. M. Lorenz, R. Voll, M. Grünke, W. Woith, and J. R. Kalden, “A rapid and simple method for the isolation of apoptotic DNA fragments,” Nucleic Acids Res. 22, 5506–5507 (1994).
H. Suzuki, T. Toyooka, and Y. Ibuki, “Simple and easy method to evaluate uptake potential of nanoparticles in mammalian cells using a flow cytometric light scatter analysis Environ,” Sci. Technol. 41, 3018–3024 (2007).
A. S. Pavlova, P. E. Vorob’ev, and V. F. Zarytova, “Direct site-specific dissipation of two-chained DNA by means of bleomycin conjugates A5 with triplex forming oligonucleotide,” Bioorgan. Khim. 35, 215–225 (2009).
D. Gimonet, E. Landais, H. Bobichon, P. Coninx, and F. Liautaud-Roger, “Induction of apoptosis by bleomycin in p53-null HL-60 leukemia cells,” Int. J. Oncol. 24, 313–319 (2004).
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © N.V. Shatskaya, A.S. Levina, M.N. Repkova, S.I. Baiborodin, N.V. Shikina, Z.R. Ismagilov, V.F. Zarytova, 2013, published in Rossiiskie Nanotekhnologii, 2013, Vol. 8, Nos. 3–4.
Rights and permissions
About this article
Cite this article
Shatskaya, N.V., Levina, A.S., Repkova, M.N. et al. Delivery of bleomycin A5 into cells using TiO2 nanoparticles to enhance the degradation of intracellular DNA. Nanotechnol Russia 8, 277–282 (2013). https://doi.org/10.1134/S1995078013020134
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1995078013020134