Communication
ChemComm
To verify the biocompatibility of aminonucleoside phos-
pholipids, we added DPPAdT or DOPAdT to the culture of
Human Embryonic Kidney 293 cells, and cell proliferation
was measured using a cell counting kit-8 (CCK-8). According
P. G. A. Janssen, A. Kaeser and A. P. H. J. Schenning, Chem.
Commun., 2011, 47, 4340; (d) X. Yan, P. Zhu, J. Fei and J. Li,
Adv. Mater., 2010, 22, 1283; (e) X. Yan, J. Li and H. M o¨ hwald, Adv.
Mater., 2012, 24, 2663; ( f ) F. Zhao, G. Shen, C. Chen, R. Xing,
Q. Zou, G. Ma and X. Yan, Chem. – Eur. J., 2014, 20, 6880.
1
5
2 (a) M. Rosoff, Vesicles, Marcel Dekker Inc., New York, 1996;
to the CCK-8 assay shown in Table S2 (ESI†) and Fig. S5
ESI†), after being incubated with aminonucleoside phospholipids
(
b) D. J. Hanahan, A Guide to Phospholipid Chemistry, Oxford Uni-
(
versity Press, New York, 1997; (c) Phospholipids Handbook, ed.
G. Cevc, Marcel Dekker, New York, 1993.
(a) D. D. Lasic, Liposomes in Gene Delivery, CRC Press, New York,
for 24 h, the cell viability remained nearly 100%, and the addition
of DOPAdT at a concentration of 100 mM even stimulated the cell
proliferation. These results proved that aminonucleoside phos-
pholipids are fully biocompatible.
3
1
997; (b) H. X. Wang, W. Chen, H. Y. Xie, X. Y. Wei, S. Y. Yin,
L. Zhou, X. Xu and S. S. Zheng, Chem. Commun., 2014, 50, 7806;
(c) S. P. Patil, H. S. Jeong and B. H. Kim, Chem. Commun., 2012,
4
1
8, 8901; (d) M. A. Mintzer and E. E. Simanek, Chem. Rev., 2009,
09, 259.
Evaluation of the cellular uptake of aminonucleoside phos-
pholipids was performed by encapsulating coumarin as the
4
5
P. R. Dash, M. L. Read, L. B. Barrett, M. A. Wolfert and L. W.
Seymour, Gene Ther., 1999, 6, 643.
16
fluorescent probe. As shown in Fig. S6 and S7 (ESI†), after 4 h
incubation, the fluorescence intensities of MCF-7 breast cancer
cells after applying free coumarin, coumarin-phosphatidylcholine
(a) P. Barth ´e l ´e my, C. R. Chim., 2009, 12, 171; (b) H. Rosemeyer,
Chem. Biodiversity, 2005, 2, 977; (c) A. Gissot, M. Camplo, M. W.
Grinstaff and P. Barth ´e l ´e my, Org. Biomol. Chem., 2008, 6, 1324;
(d) L. Moreau, P. Barth ´e l ´e my, M. E. Maataoui and M. W. Grinstaff,
J. Am. Chem. Soc., 2004, 126, 7533; (e) L. Moreau, M. W. Grinstaff and
P. Barth ´e l ´e my, Tetrahedron Lett., 2005, 46, 1593; ( f ) L. Moreau,
N. Campins, M. W. Grinstaff and P. Barth ´e l ´e my, Tetrahedron Lett.,
2006, 47, 7117; (g) N. Campins, P. Dieudonn ´e , M. W. Grinstaff and
P. Barth ´e l ´e my, New J. Chem., 2007, 31, 1928; (h) I. Bestel,
N. Campins, A. Marchenko, D. Fichou, M. W. Grinstaff and
P. Barth ´e l ´e my, J. Colloid Interface Sci., 2008, 323, 435; (i) C. Heiz,
U. R ¨a dler and P. L. Luisi, J. Phys. Chem. B, 1998, 102, 8686;
(EPC) liposomes, coumarin-DOPAdT liposomes and blank
medium were 224, 245, 317 and 5, respectively. These results
demonstrated that DOPAdT liposomes significantly enhanced
the cellular uptake of coumarin, exhibiting high transmembrane
capability.
In the study of transfecting polyA, however, the result was
not parallel to coumarin. It could be due to the electrostatic
repulsion of phosphate anions between polyA and DOPAdT
relatively hindering the interaction of gene and materials, for
which the potential value of liposomes was ꢀ31 mV. New
thymine-glyceride analogues based on DOPAdT excluding the
phosphate moiety are yet to be developed to improve the
efficient delivery of gene drugs in further research.
In conclusion, we have developed a novel class of amino-
nucleoside phospholipids, which spontaneously assemble into
various supramolecular structures in aquatic media, including
multilamellar organization, hydrogels, superhelical strands,
and vesicles. These molecules have good biocompatibility, high
transmembrane capability, and can form complexes with sin-
gle- and double-stranded DNA by p–p stacking and hydrogen
bond networks. This work has opened up interesting avenues
for the development of novel supramolecular systems, and for
the design and use of novel non-viral vectors in gene delivery.
Further studies on the application of aminonucleoside phos-
pholipids in gene delivery are ongoing in this laboratory.
This research was supported by Ministry of Science and Techno-
logy of China (2012CB720604, 2012AA022501), and Scholarship
(
j) M. Skwarczynski, Z. M. Ziora, D. J. Coles, I.-C. Lin and I. Toth,
Chem. Commun., 2010, 46, 3140; (k) M. Banchelli, D. Berti and
P. Baglioni, Angew. Chem., Int. Ed., 2007, 46, 3070; (l) S. Milani,
F. B. Bombelli, D. Berti and P. Baglioni, J. Am. Chem. Soc., 2007,
129, 11664; (m) L. Moreau, M. Camplo, M. Wathier, N. Taib,
M. Laguerre, I. Bestel, M. W. Grinstaff and P. Barth ´e l ´e my, J. Am.
Chem. Soc., 2008, 130, 14454.
6 (a) D. Pan, C. Tang, X. Fan, Y. Li, X. Yang, H. Jin, Z. Guan, Z. Yang
and L. Zhang, New J. Chem., 2013, 37, 1122; (b) X. X. Li, L. R. Zhang,
J. F. Lu, Y. Z. Chen, J. M. Min and L. H. Zhang, Bioconjugate Chem.,
2
003, 14, 153; (c) C. P. Chen, L. R. Zhang, Y. F. Peng, X. B. Wang,
S. Q. Wang and L. H. Zhang, Bioconjugate Chem., 2003, 14, 532;
d) Y. Liu, X. F. Wang, Y. Chen, L. H. Zhang and Z. J. Yang,
(
MedChemComm, 2012, 3, 506.
I. van Daele, H. Munier-Lehmann, M. Froeyen, J. Balzarini and
S. van Calenbergh, J. Med. Chem., 2007, 50, 5281.
(a) Y. Kazushige, N. Yoshitaka, N. Kazuo, Y. Tetsuya, N. Kenichi,
N. Hidehiko and S. Osamu, Tetrahedron Lett., 1991, 32, 4721;
7
8
(
b) B. H. Dahl, J. Nielsen and O. Dahl, Nucleic Acids Res., 1987,
15, 1729.
9
D. W. Pack, G. Chen, K. M. Maloney, C.-T. Chen and F. H. Arnold,
J. Am. Chem. Soc., 1997, 119, 2479.
0 (a) K. Y. Lee and D. J. Mooney, Chem. Rev., 2001, 101, 1869;
1
(b) L. A. Estroff and A. D. Hamilton, Chem. Rev., 2004, 104, 1201;
(
(
c) Z. Yang, G. Liang and B. Xu, Acc. Chem. Res., 2008, 41, 315;
d) A. R. Hirst, B. Escuder, J. F. Miravet and D. K. Smith, Angew.
Chem., Int. Ed., 2008, 47, 8002.
Award for Excellent Doctoral Student Granted by Ministry of Educa- 11 J.-H. Fuhrhop and W. Helfrich, Chem. Rev., 1993, 93, 1565.
1
1
1
2 Y. Cohen, L. Avram and L. Frish, Angew. Chem., Int. Ed., 2005,
4, 520.
tion. The authors thank Dr Xue Qiao of Peking University, Dr Prof.
Yong Chen and Dr Ying-Ming Zhang of Nankai University, for their
kind advice and help in this study.
4
3 W. Saenger, Principles of Nucleic Acid Structure, Spring-Verlag, New
York, 1984.
4 (a) Y. Liu, L. Yu, Y. Chen, Y.-L. Zhao and H. Yang, J. Am. Chem. Soc.,
2
007, 129, 10656; (b) Y. Liu, Z.-L. Yu, Y.-M. Zhang, D.-S. Guo and Y.-P.
Notes and references
Liu, J. Am. Chem. Soc., 2008, 130, 10431.
15 M. Ishiyama, H. Tominaga, M. Shiga, K. Sasamoto, Y. Ohkura and
1
(a) T. L. Hill, Linear Aggregation Theory in Cell Biology, Springer-
Verlag, New York, 1987; (b) A. Kumar, J. H. Hwang, S. Kumar and 16 X.-X. Wang, Y.-B. Li, H.-J. Yao, R.-J. Ju, Y. Zhang, R.-J. Li, Y. Yu,
J. M. Nam, Chem. Commun., 2013, 49, 2597; (c) A. R. Carretero, L. Zhang and W.-L. Lu, Biomaterials, 2011, 32, 5673.
K. Ueno, Biol. Pharm. Bull., 1996, 19, 1518.
472 | Chem. Commun., 2015, 51, 469--472
This journal is ©The Royal Society of Chemistry 2015