**8. References**


Bioreducible Cationic Polymers for Gene Transfection 101

Koo, H., Jin, G., Kang, H., Lee, Y., Nam, K., Zhe, B.C. & Park, J.S. (2010). Biodegradable

Kukowska-Latallo, J.F., Bielinska, A.U. & Johnson, J. (1996). Efficient Transfer of Genetic

Lee, Y., Mo, H., Koo, H., Park, J.Y., Cho, M.Y., Jin, G.W. & Park, J.S. (2007). Visualization of

Li, F., Liu, W.G. & Yao, K.D. (2002). Preparation of Oxidized Glucose-Crosslinked N-

Lim, Y.B., Choi, Y.H. & Park, J.S. (1999). A Self-Destroying Polycationic Polymer:

Lim, Y.B., Kim, C.H., Kim, K., Kim, S.W. & Park, J.S. (2000). Development of a Safe Gene

Lin, C., Zhong, Z.Y., Lok, M.C., Jiang, X., Hennink, W.E., Feijen, J. & Engbersen, J.F.J. (2006).

Lin, C., Zhong, Z.Y., Lok, M.C., Jiang, X., Hennink, W.E., Feijen, J. & Engbersen, J.F.J.

Lin, C., Zhong, Z.Y., Lok, M.C., Xulin Jiang, Wim E. Hennink, Feijen, J. & Engbersen, J.F.J.

Lin, C., Blaauboer, C.-J., Timoneda, M.M., Lok, M.C., van Steenbergen, M., Hennink, W.E.,

Lin, C. & Engbersen, J.F.J. (2008). Effects of Chemical Functionalities in Poly(Amido

Liu, J., Jiang, X., Xu, L., Wang, X., Hennink, W.E. & Zhuo, R. (2010). Novel Reduction-

No.3, (December 2008), pp. 267-272, ISSN 0168-3659

*Society,* Vol.121, No.24, (June 1999), pp. 5633-5639, ISSN 0002-7863

(February 2010), pp. 988-997, ISSN 0142-9612

13-18, ISSN 1043-1802

pp. 6524-6525, ISSN 0002-7863

2007a), pp. 67-75, ISSN 0168-3659

137, ISSN 0168-3659

145, ISSN 1043-1802

174, ISSN 0168-3659

No.10, (May 1996), pp. 4897-4902, ISSN 0027-8424

Vol.7, No.1, (January 2000), pp. 31-34, ISSN 0969-7128

Branched Poly(Ethylenimine Sulfide) for Gene Delivery. *Biomaterials,* Vol.31, No.5,

Material into Mammalian Cells Using Starburst Polyamioamine Dendrimers. *Proceedings of the National Academy of Sciences of the United States of America,* Vol.93

the Degradation of a Disulfide Polymer, Linear Poly(Ethylenimine Sulfide), for Gene Delivery. *Bioconjugate Chemistry,* Vol.18 No.1, (January-February 2007), pp.

Alkylated Chitosan Membrane and in Vitro Studies of pH-Sensitive Drug Delivery Behavior. *Biomaterials,* Vol.23, No.2, (January 2002), pp. 343-347, ISSN 0142-9612 Li, S. & Huang, L. (2000). Non-Viral Gene Therapy: Promises and Challenges. *Gene Therapy,*

Biodegradable Poly(4-Hydroxy-L-Proline Ester). *Journal of the American Chemical* 

Delivery System Using Biodegradable Polymer, Poly[Alpha-(4-Aminobutyl)-L-Glycolic Acid]. *Journal of the American Chemical Society,* Vol.122, No.4, (June 2000),

Linear Poly(Amido Amine)S with Secondary and Tertiary Amino Groups and Variable Amounts of Disulfide Linkages: Synthesis and in Vitro Gene Transfer Properties. *Journal of Controlled Release,* Vol.116, No.2, (November 2006), pp. 130-

(2007a). Random and Block Copolymers of Bioreducible Poly(Amido Amine)S with High- and Low-Basicity Amino Groups: Study of DNA Condensation and Buffer Capacity on Gene Transfection. *Journal of Controlled Release,* Vol.123, No.1, (October

(2007b). Novel Bioreducible Poly(Amido Amine)S for Highly Efficient Gene Delivery. *Bioconjugate Chemistry,* Vol.18, No.1, (January-February 2007b), pp. 138-

Feijen, J., Zhong, Z.Y. & Engbersen, J.F.J. (2008). Bioreducible Poly(Amido Amine)S with Oligoamine Side Chains: Synthesis, Characterization, and Structural Effect on Gene Delivery. *Journal of Controlled Release,* Vol.126, No.2, (March 2008), pp. 166-

Amine)S for Non-Viral Gene Transfection. *Journal of Controlled Release,* Vol.132,

Responsive Cross-Linked Polyethylenimine Derivatives by Click Chemistry for

Polycations in Gene Transfer. *Journal of Gene Medicine,* Vol.6, No.10, (October 2004 ), pp. 1102-1111, ISSN 1099-498X


Boussif, O., Lezoualch, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B. & Behr,

Breunig, M., Lungwitz, U., Liebl, R. & Goepferich, A. (2007). Breaking up the Correlation

Choi, S. & Lee, K.D. (2008). Enhanced Gene Delivery Using Disulfide-Crosslinked Low

de Smedt, S.C., Demeester, J. & Hennink, W.E. (2000). Cationic Polymer Based Gene

El-Aneed, A. (2004). An Overview of Current Delivery Systems in Cancer Gene Therapy. *J* 

Ganta, S., Devalapally, H., Shahiwala, A. & Amiji, M. (2008). A Review of Stimuli-

Gao, Y., Chen, L., Zhang, Z., Chen, Y. & Li, Y. (2010). Reversal of Multidrug Resistance by

Godbey, W.T., Wu, K.K. & Mikos, A.G. (2001). Poly(Ethylenimine)-Mediated Gene Delivery

Gorlich, D. & Kutay, U. (1999). Transport between the Cell Nucleus and the Cytoplasm.

Gosselin, M.A., Guo, W. & Lee, R.J. (2001). Efficient Gene Transfer Using Reversibly Cross-

Gosselin, M.A., Guo, W. & Lee, R.J. (2002). Incorporation of Reversibly Cross-Linked

Jeong, J.H., Kim, S.W. & Park, T.G. (2007). Molecular Design of Functional Polymers for

Jere, D., Kim, J.E., Arote, R., Jiang, H.L., Kim, Y.K., Choi, Y.J., Yun, C.H., Cho, M.H. & Cho,

No.6, (November-December 2001), pp. 989-994, ISSN 1043-1802

No.5, (September-October 2002), pp. 1044-1053, ISSN 1043-1802

(September 2007), pp. 14454-14459, ISSN 0027-8424

Vol.126, No.3, (March 2008), pp. 187-204, ISSN 0168-3659

pp. 1102-1111, ISSN 1099-498X

ISSN 0027-8424

70-76, ISSN 0168-3659

126, ISSN 1043-6618

9612

*Control Rel,* Vol.94, No.2004), pp. 1-14,

2001), pp. 471-480, ISSN 0142-9612

607-660, ISSN 1081-0706

1239-1274, ISSN 0079-6700

(March 2009), pp. 1635-1647, ISSN 0142-9612

Polycations in Gene Transfer. *Journal of Gene Medicine,* Vol.6, No.10, (October 2004 ),

J.P. (1995). A Versatile Vector for Gene and Oligonucleotide Transfer into Cells in Culture and in Vivo: Polyethylenimine. *Proceedings of the National Academy of Sciences of the United States of America,* Vol.92, No.16, (August 1995), pp. 7297-7301,

between Efficacy and Toxicity for Nonviral Gene Delivery. *Proceedings of the National Academy of Sciences of the United States of America,* Vol.104, No.36,

Molecular Weight Polyethylenimine with Listeriolysin O-Polyethylenimine Disulfide Conjugate. *Journal of Controlled Release,* Vol.131, No.1, (October 2008), pp.

Delivery Systems. *Pharmaceutical Research,* Vol.17, No.2, (February 2000), pp. 113-

Responsive Nanocarriers for Drug and Gene Delivery. *Journal of Controlled Release,*

Reduction-Sensitive Linear Cationic Click Polymer/iMDR1-pDNA Complex Nanoparticles. *Biomaterials,* Vol.32, No.6, (February 2010), pp. 1738-1747, ISSN 0142-

Affects Endothelial Cell Function and Viability. *Biomaterials,* Vol.22, No.5, (March

*Annual Review of Cell and Developmental Biology,* Vol.15, No.1, (January 1999), pp.

Linked Low Molecular Weight Polyethylenimine. *Bioconjugate Chemistry,* Vol.12,

Polyplexes into LPDII Vectors for Gene Delivery. *Bioconjugate Chemistry,* Vol.13,

Gene Therapy. *Progress in Polymer Science,* Vol.32 No.11, (November 2007), pp.

C.S. (2009). Akt1 Silencing Efficiencies in Lung Cancer Cells by Sh/Si/Ssirna Transfection Using a Reductable Polyspermine Carrier. *Biomaterials,* Vol.30, No.8,


Bioreducible Cationic Polymers for Gene Transfection 103

Pack, D.W., Hoffman, A.S., Pun, S. & Stayton, P.S. (2005). Design and Development of

Peng, Q., Zhong, Z.L. & Zhuo, R.X. (2008). Disulfide Cross-Linked Polyethylenimines (PEI)

Pichon, C., LeCam, E., Guerin, B., Coulaud, D., Delain, E. & Midoux, P. (2002). Poly [Lys-

*Chemistry,* Vol.13, No.1, (January-February 2002), pp. 76-82, ISSN 1043-1802 Putnam, D., Gentry, C.A., Pack, D.W. & Langer, R. (2001). Polymer-Based Gene Delivery

Read, M.L., Singh, S., Ahmed, Z., Stevenson, M., Briggs, S.S., Oupicky, D., Barrett, L.B., Spice,

Sato, T., Ishii, T. & Okahata, Y. (2002). In Vitro Gene Delivery Mediated by Chitosan. Effect

*Biomaterials,* Vol.22, No.15, (August 2002), pp. 2075-2080, ISSN 0142-9612 Sirirat, C., Lobo, B.A., Koe, G.S., Koe, J.G. & Middaugh, C.R. (2003). Biophysical

Son, S., Singha, K. & Kim, W.J. (2010). Bioreducible BPEI-SS-PEG-cNGR Polymer as a Tumor

Soundara, M.D. & Oupicky, D. (2006). Polyplex Gene Delivery Modulated by Redox

Suh, J., Wirtz, D. & Hanes, J. (2003). Efficient Active Transport of Gene Nanocarriers to the

Sun, Y.X., Zeng, X., Meng, Q.F., Zhang, X.Z., Cheng, S.X. & Zhuo, R.X. (2008). The Influence

Szoka, F.C.J. (1993). Polyamidoamine Cascade Polymers Mediate Efficient Transfection of

*America,* Vol.100, No.7, (April 2003), pp. 3878-3882, ISSN 0027-8424

No.8, (August 2003), pp. 1710-1722, ISSN 0022-3549

(January 2002), pp. 8-9, ISSN 0002-7863

2001), pp. 1200-1205, ISSN 0027-8424

pp. 361-371, ISSN 0955-0674

6344-6354, ISSN 0142-9612

pp. 4356-4365, ISSN 0142-9612

372-379, ISSN 1043-1802

526, ISSN 1061-186X

pp. 589-593, ISSN 1474-1776

1043-1802

of DNA Delivery Vectors. *Journal of the American Chemical Society,* Vol.124, No.1,

Polymers for Gene Delivery. *Nature Reviews Drug Discovery,* Vol.4, No.7, (July 2005),

Prepared Via Thiolation of Low Molecular Weight PEI as Highly Efficient Gene Vectors. *Bioconjugate Chemistry,* Vol.19, No.2, (February 2008), pp. 499-506, ISSN

(AEDTP)]: A Cationic Polymer That Allows Dissociation of Pdna/Cationic Polymer Complexes in a Reductive Medium and Enhances Polyfection. *Bioconjugate* 

with Low Cytotoxicity by a Unique Balance of Side-Chain Termini. *Proceedings of the National Academy of Sciences of the United States of America,* Vol.98, No.3, (January

R., Kendall, M., Berry, M., Preece, J.A., Logan, A. & Seymour, L.W. (2005). A Versatile Reducible Polycation-Based System for Efficient Delivery of a Broad Range of Nucleic Acids. *Nucleic Acid Research,* Vol.33, No.24, (May 2005), pp. e86, ISSN 0305-1048 Ryan, K.J. & Wente, S.R. (2000). The Nuclear Pore Complex: A Protein Machine Bridging the

Nucleus and Cytoplasm. *Curruent Opinion in Cell Biology,* Vol.12, No.3, (June 2000),

of pH, Serum, and Molecular Mass of Chitosan on the Transfection Efficiency.

Characterization of PEI/DNA Complexes. *Journal of Pharmaceutical Science,* Vol.92,

Targeted Nonviral Gene Carrier. *Biomaterials,* Vol.31, No.24, (August 2010), pp.

Potential Gradients. *Journal of Drug Target,* Vol.14, No.8, (September 2006), pp. 519-

Cell Nucleus. *Proceedings of the National Academy of Sciences of the United States of* 

of Rgd Addition on the Gene Transfer Characteristics of Disulfide-Containing Polyethyleneimine/DNA Complexes. *Biomaterials,* Vol.29, No.32, (November 2008),

Cells in Culture. *Bioconjugate Chemistry,* Vol.4, No.5, (September-October 1993), pp.

Nonviral Gene Delivery. *Bioconjugate Chemistry,* Vol.21, No.10, (October 2010), pp. 1827-1835, ISSN 1043-1802


Liu, W.G. & Yao, K.D. (2002). Chitosan and Its Derivatives-a Promising Non- Viral Vector

Luo, D. & Saltzman, W.M. (2000). Synthetic DNA Delivery Systems. *Nature Biotechnology,*

Luten, J., van Steenis, J.H. & van Someren, R. (2003). Water-Soluble Biodegradable Cationic

Luten, J., van Nostruin, C.F., De Smedt, S.C. & Hennink, W.E. (2008). Biodegradable

Lynn, D.M. & Langer, R. (2000). Degradable Poly(Β-Amino Esters): Synthesis,

Mishra, S., Webster, P. & Davis, M.E. (2004). Pegylation Significantly Affects Cellular Uptake

Morre, D.J. & Morre, D.M. (2003). Cell Surface NADH Oxidases (ECTO-NOX Proteins) with

Mumper, R.J., Wang, J., Claspell, J.M. & Rolland, A.P. (1995). Novel Polymeric Condensing

Neu, M., Germershaus, O., Behe, M. & Kissel, T. (2007a). Bioreversibly Crosslinked

Neu, M., Germershaus, O., Mao, S., Voigt, K., Behe, M. & Kissel, T. (2007b). Crosslinked

Nishikawa, M. & Huang, L. (2001). Nonviral Vectors in the New Millennium: Delivery

Oupicky, D., Parker, A.L. & Seymour, L.W. (2002). Laterally Stabilized Complexes of DNA

Vol.118, No.3, (April 2007b), pp. 370-380, ISSN 0168-3659

*of Cell Biology,* Vol.83, No.3, (April 2004), pp. 97-111, ISSN 0171-9335 Moghimi, S.M., Symonds, P., Murray, J.C., Hunter, A.C., Dekska, G. & Szewczyk, A. (2005).

*Release,* Vol.126, No.2, (March 2008), pp. 97-110, ISSN 0168-3659

Vol.18, No.1, (January 2000), pp. 33-37, ISSN 1087-0156

No.5, (September 2002), pp. 715-758, ISSN 0169-409X

(May 2003), pp. 483-497, ISSN 0168-3659

1827-1835, ISSN 1043-1802

pp. 1-11, ISSN 0168-3659

1525-0016

30-August 4, 1995

69-80, ISSN 0168-3659

870, ISSN 0305-1048

5762

Nonviral Gene Delivery. *Bioconjugate Chemistry,* Vol.21, No.10, (October 2010), pp.

for Gene Transfection. *Journal of Controlled Release,* Vol.83, No.1, (September 2002),

Polyphosphazenes for Gene Delivery. *Journal of Controlled Release,* Vol.89, No.3,

Polymers as Non-Viral Carriers for Plasmid DNA Delivery. *Journal of Controlled* 

Characterization, and Self-Assembly with Plasmid DNA. *Journal of the American Chemical Society,* Vol.122, No.44, (October 2000), pp. 10761-10768, ISSN 0002-7863 Merdan, T., Kopecek, J. & Kissel, T. (2002). Prospects for Cationic Polymers in Gene and

Oligonucleotide Therapy against Cancer. *Advanced Drug Delivery Review,* Vol.54,

and Intracellular Trafficking of Non-Viral Gene Delivery Particles. *European Journal* 

A Two-Stage Poly(Ethylenimine)-Mediated Cytotoxicity: Implications for Gene Transfer/Therapy. *Molecular Therapy,* Vol.11, No.6, (June 2005), pp. 990-995, ISSN

Roles in Cancer, Cellular Time-Keeping, Growth, Aging and Neurodegenerative Diseases. *Free Radical Research,* Vol.37, No.8, (August 2003), pp. 795-808, ISSN 1071-

Carriers for Gene Delivery. *Proceedings of the 21st International Symposium of Controlled Release of Bioactive Materials,* ISBN 0849351812, Seattle, Washington, July

Polyplexes of PEI and High Molecular Weight PEG Show Extended Circulation Times in Vivo. *Journal of Controlled Release,* Vol.124, No.1-2, (December 2007a), pp.

Nanocarriers Based Upon Poly(Ethylene Imine) for Systemic Plasmid Delivery: In Vitro Characterization and in Vivo Studies in Mice. *Journal of Controlled Release,*

Barriers in Gene Transfer. *Nucleic Acid Research,* Vol.12 No.8, (May 2001), pp. 861-

with Linear Reducible Polycations: Strategy for Triggered Intracellular Activation

of DNA Delivery Vectors. *Journal of the American Chemical Society,* Vol.124, No.1, (January 2002), pp. 8-9, ISSN 0002-7863


**5** 

Vitaly K. Koltover

 *Russian Federation* 

*Chernogolovka, Moscow Region,* 

**Stable Magnetic Isotopes as a** 

*Institute of Problems of Chemical Physics, Russian Academy of Sciences,* 

Diverse organisms possess the ability to perceive Earth's magnetic field, the strength of which is about 0.05 mT (Lohmann, 2010; Gould, 2010). There exist magnetotactic bacteria the ability of which to use geomagnetic fields for direction sensing is accomplished owing to the so-called magnetosomes, the specific nanometer-sized magnetite particles organized into

However, apart from external magnetic fields, another variety of natural magnetism is around, namely, magnetic fields of atomic nuclei of magnetic isotopes. Some of them produce intramolecular magnetic fields which are 10-100 times greater than terrestrial (Grant & Harris, 1996). This raises the question of whether living cells can perceive the difference between magnetic and non-magnetic isotopes of the same chemical element. There is also a practical issue of whether the cell can take advantage of the magnetic

The present article is a mini-review of the works of our group in this direction. The premises for our research have been the findings of magnetic-isotope effect (MIE) in chemical and biochemical physics within recent years (Brocklenhurst, 2002; Buchachenko, 2009). Following the concept of "nuclear spin catalysis in biopolymer nanoreactors" (Koltover, 2007, 2008), in experiments with bacteria *Escherichia coli*, the commonly accepted microbial model, we have revealed that the cells enriched with magnetic 25Mg demonstrate essentially higher viability by comparison to the cells enriched with the nonmagnetic isotopes of magnesium (Bogatyrenko et al., 2009a, 2009b; Koltover et al., 2012). Furthermore, in experiments with *Saccharomyces cerevisiae*, another standard cell model, we have revealed that the magnetic isotope of 25Mg, by comparison to nonmagnetic isotope 24Mg, is essentially more effective stimulator of the recovery processes in the yeast cells after short-wave UV irradiation. The rate of post-radiation recovery was found to be twice as good for the cells enriched with 25Mg as compared to the cells enriched with nonmagnetic isotope (Grodzinsky et al, 2011). Thus, the magnetic-isotope effects have been revealed, for the first time, *in viv*o. It opens up a new way in biomedicine, based on the stable magnetic isotopes, namely, the novel preventive medicine including new, 25Mg-based, anti-stress drugs as well

**1. Introduction** 

isotopes.

chains within the cell (Komeili, 2007).

as anti-aging and anti-radiation protectors.

**New Trend in Biomedicine** 

