Journal of the American Chemical Society
Communication
T.; Roulier, I.; Eisenberg, A. J. Am. Chem. Soc. 2009, 131, 10557.
(c) Ahmed, F.; Pakunlu, R. I.; Brannan, A.; Bates, F.; Minko, T.;
Discher, D. E. J. Controlled Release 2006, 116, 150. (d) Bellomo, E. G.;
Wyrsta, M. D.; Pakstis, L.; Pochan, D. J.; Deming, T. J. Nat. Mater.
2004, 3, 244. (e) Robbins, G. P.; Jimbo, M.; Swift, J.; Therien, M. J.;
Hammer, D. A.; Dmochowski, I. J. J. Am. Chem. Soc. 2009, 131, 3872.
(8) Kim, K. T.; Meeuwissen, S. A.; Nolte, R. J. M.; van Hest, J. C. M.
Nanoscale 2010, 2, 844.
triggering by monosaccharide binding. Also, the presence of
nonbinding diols such as ethylene glycol in the medium (up to
1 M) did not cause significant disassembly of the polymer-
somes. The polymersomes, as examined by DLS, stayed intact
during 2 days of dialysis in the presence of 1 M ethylene glycol.
As suggested by previous studies,17,18 nonreducing sugars such
as α-methyl-D-mannopyranoside also induced disassembly of
the polymersomes, as indicated by the release of F-insulin. In
the presence of monosaccharides, 50% of the release of insulin
from the polymersomes of 7 was achieved within 1.4 h with 0.1
M fructose and 10.5 h with 0.3 M glucose.
In summary, we have synthesized a boroxole-based styrenic
monomer that can be polymerized by the RAFT method. The
controlled polymerization of the boroxole-based monomer 1
with a PEG-based chain-transfer agent allowed us to synthesize
well-defined monosaccharide-responsive block copolymers. By
utilizing the sugar-responsive disassembly of polymersomes of
PEG-b-PBOx in aqueous solution at neutral pH, we have
demonstrated the monosaccharide-triggered disassembly of
polymersomes to release encapsulated cargo molecules such as
FITC-labeled insulin under physiologically relevant pH
conditions. Encapsulated insulin was released from the
polymersomes only in response to the presence of mono-
saccharides that bind to boroxole moieties. The boroxole-
containing polymers and block copolymers reported here may
find applications in the development of sensors and drug
delivery systems designed for glucose-related human diseases
such as diabetes. We are currently working on designing new
self-assembling boronic acid-containing block copolymers to
improve the binding efficiency and selectivity toward glucose23
under physiological conditions.
(9) Nishiyabu, R.; Kubo, Y.; James, T. D.; Fossey, J. S. Chem.
Commun. 2011, 47, 1106.
(10) (a) Cambre, J. N.; Sumerlin, B. S. Polymer 2011, 52, 4631.
(b) Cheng, F.; Jakle, F. Polym. Chem. 2011, 2, 2122. (c) Jakle, F. Chem.
̈
̈
Rev. 2010, 110, 3985. (d) Kanekiyo, Y.; Sano, M.; Iguchi, R.; Shinkai,
S. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 1302.
(11) (a) Kataoka, K.; Miyazaki, H.; Bunya, M.; Okano, T.; Sakurai, Y.
J. Am. Chem. Soc. 1998, 120, 12694. (b) Matsumoto, A.; Yoshida, R.;
Kataoka, K. Biomacromolecules 2004, 5, 1038. (c) Matsumoto, A.;
Yamamoto, K.; Yoshida, R.; Kataoka, K.; Aoyagi, T.; Miyahara, Y.
Chem. Commun. 2010, 46, 2203.
(12) (a) Cambre, J. N.; Roy, D.; Gondi, S. R.; Sumerlin, B. S. J. Am.
Chem. Soc. 2007, 129, 10348. (b) Roy, D.; Cambre, J. N.; Sumerlin, B.
S. Chem. Commun. 2008, 2477. (c) Kim, K. T.; Cornelissen, J. J. L. M.;
Nolte, R. J. M.; van Hest, J. C. M. Adv. Mater. 2009, 21, 2787.
(d) Bapat, A. P.; Roy, D.; Ray, J. G.; Savin, D. A.; Sumerlin, B. S. J. Am.
Chem. Soc. 2011, 133, 19832. (e) Sumerlin, B. S.; Camber, J. N.; Roy,
D. U.S. Pat. Appl. US 2010/0029545 A1, 2010.
(13) Wu, Q.; Wang, L.; Yu, H.; Wang, J.; Chen, Z. Chem. Rev. 2011,
111, 7855.
(14) Wulff, G. Pure Appl. Chem. 1982, 54, 2093.
(15) Kim, K. T.; Cornelissen, J. J. L. M.; Nolte, R. J. M.; van Hest, J.
C. M. J. Am. Chem. Soc. 2009, 131, 13908.
(16) (a) Mulla, H. R.; Agard, N. J.; Basu, A. Bioorg. Med. Chem. Lett.
2004, 14, 25. (b) Matsumoto, A.; Ishii, T.; Nishida, J.; Matsumoto, H.;
Kataoka, K.; Miyahara, Y. Angew. Chem., Int. Ed. 2012, DOI: 10.1002/
anie.201106252. (c) Li, Y.; Xiao, W.; Xiao, K.; Berti, L.; Luo, J.; Tseng,
H. P.; Fung, G.; Lam, K. S. Angew. Chem., Int. Ed. 2012,
DOI: 10.1002/anie.201107144.
ASSOCIATED CONTENT
* Supporting Information
■
S
(17) (a) Dowlut, M.; Hall, D. G. J. Am. Chem. Soc. 2006, 128, 4226.
Detailed experimental procedures, characterization data, and
supporting figures. This material is available free of charge via
(b) Ber
(c) Pal, A.; Ber
1492.
́
ube,
́
M.; Dowlut, M.; Hall, D. G. J. Org. Chem. 2008, 73, 6471.
́
ube, M.; Hall, D. G. Angew. Chem., Int. Ed. 2010, 49,
́
(18) (a) Jay, J. I.; Lai, B. E.; Myszka, D. G.; Mahalingam, A.;
Langheinrich, K.; Katz, D. F.; Kiser, P. F. Mol. Pharmaceutics 2010, 7,
116. (b) Mahalingam, A.; Geonnotti, A. R.; Balzarini, J.; Kiser, P. F.
Mol. Pharmaceutics 2011, 8, 2465.
(19) Springsteen, G.; Wang, B. Chem. Commun. 2001, 1608.
(b) Springsteen, G.; Wang, B. Tetrahedron 2002, 58, 5291.
AUTHOR INFORMATION
Corresponding Author
■
Notes
(20) Qin, Y.; Sukul, V.; Pagakos, D.; Cui, C.; Jakle, F. Macromolecules
̈
The authors declare no competing financial interest.
2005, 38, 8987.
(21) Lai, J. T.; Filla, D.; Shea, R. Macromolecules 2002, 35, 6754.
(22) Huang, C.-Q.; Pan, C.-Y. Polymer 2010, 51, 5115.
(23) (a) Shimpuku, C.; Ozawa, R.; Sasaki, A.; Sato, F.; Hashimoto,
T.; Yamauchi, A.; Suzuki, I.; Hayashita, T. Chem. Commun. 2009, 1709.
(b) Yang, W.; He, H.; Drueckhammer, D. G. Angew. Chem., Int. Ed.
2001, 40, 1714. (c) Eggert, H.; Frederiksen, J.; Morin, C.; Norrild, J.
C. J. Org. Chem. 1999, 64, 3846.
ACKNOWLEDGMENTS
■
This work was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF)
funded by the Korean Government (MEST) (2011-0026460).
We thank Prof. Jongnam Park for the help with SEC
experiments and Dr. E.-K. Kim and UOBC for fluorescence
microscopy.
REFERENCES
■
(1) Tanner, P.; Baumann, P.; Enea, R.; Onaca, O.; Palivan, C.; Meier,
W. Acc. Chem. Res. 2011, 44, 1039.
(2) Meng, F.; Zhong, Z. J. Phys. Chem. Lett. 2011, 2, 1533.
(3) Brinkhuis, R. P.; Rutjes, F. P. J. T.; van Hest, J. C. M. Polym.
Chem. 2011, 2, 1449.
(4) Discher, D. E.; Eisenberg, A. Science 2002, 297, 967.
(5) Meng, F.; Zhong, Z.; Feijen, J. Biomacromolecules 2009, 10, 197.
(6) Li, M.-H.; Keller, P. Soft Matter 2009, 5, 927.
(7) (a) Mabrouk, E.; Cuvelier, D.; Brochard-Wyart, F.; Nassoy, P.; Li,
M.-H. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 7294. (b) Yu, S.; Azzam,
4033
dx.doi.org/10.1021/ja211728x | J. Am. Chem. Soc. 2012, 134, 4030−4033