Macromolecules
Article
Figure 8. Time-dependent change in the normalized intensity of NR fluorescence in PF4a nanoparticles (a) at different H2O2 concentrations and
(b) at different pHs without (empty) or with (solid) H2O2 (2.0 mM), and (c) in PF3a, PF4a, and PF4b nanoparticles without (empty) or with
(solid) H2O2 (2.0 mM). NR concentration: 5 × 10−6 mol/L; 37 °C; pH 7.4.
amines but slows down the phenylboronic ester oxidation and
the subsequent self-immolative elimination.
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Figure 8c shows the degradation kinetics of PF3a, PF4a, and
PF4b nanoparticles in PB. PF3a and PF4a nanoparticles
exhibited similar degradation profiles, while PF4b nanoparticles
degraded at a much slower rate. These results might
demonstrate that the degree of PEGylation, not the molecular
weight of the polymer precursors (F3 vs F4), mainly influenced
the degradation kinetics of the copolymer nanoparticles.
Compared with PF3a or PF4a nanoparticles, the oxidation-
responsive segments in PF4b nanoparticles are located in the
more hydrophobic microdomains that have a lower perme-
ability to H2O2 as well as water molecules.21 H2O2-induced
oxidative degradation of the PF4b nanoparticles was further
confirmed by the light scattering and TEM measurements
(Figure S25).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was financially supported by the National Natural
Science Foundation of China (21174002 and 21090351) and
the National Science Fund for Distinguished Young Scholars of
China (21225416).
REFERENCES
■
(1) (a) Oktyabrsky, O.; Smirnova, G. Biochemistry (Moscow) 2007,
72, 132−145. (b) Khutoryanskiy, V. V.; Tirelli, N. Pure Appl. Chem.
2008, 80, 1703−1718. (c) Niethammer, P.; Grabher, C.; Look, A. T.;
Mitchison, T. J. Nature 2009, 459, 996−1000.
(2) (a) Coussens, L. M.; Werb, Z. Nature 2002, 420, 860−867.
(b) Winterbourn, C. C. Nat. Chem. Biol. 2008, 4, 278−286. (c) Maloy,
K. J.; Powrie, F. Nature 2011, 474, 298−306. (d) Zhou, R.; Yazdi, A.
S.; Menu, P.; Tschopp, J. Nature 2011, 469, 221−225. (e) Gupta, S.
C.; Hevia, D.; Patchva, S.; Park, B.; Koh, W.; Aggarwal, B. B. Antioxid.
Redox Signaling 2012, 16, 1295−1322.
CONCLUSION
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By combining Michael-type addition polymerization and
postmodification, a series of PEGylated poly(amino ester)s
containing phenylboronic ester were synthesized. These
oxidation/pH dual responsive amphiphilic copolymers can
self-assemble in aqueous media into nanoparticles that degrade
upon oxidation by H2O2. Based on the oxidation results of
model compounds, the degradation kinetics and products of
the copolymer nanoparticles were investigated. Increasing the
concentration of H2O2, the pH of the media, and the
PEGylation degree of the copolymers accelerated the
degradation. More importantly, the quinone methides
generated in situ during the degradation of the polymers
could be captured by the built-in secondary amino groups. Such
a feature may improve biocompatibility of the degradation
products when these polymer nanoparticles are considered for
potential in vivo application.
(3) (a) Trachootham, D.; Alexandre, J.; Huang, P. Nat. Rev. Drug
Delivery 2009, 8, 579−591. (b) Smith, D. G.; Magwere, T.; Burchill, S.
A. Expert Rev. Anticancer Ther. 2011, 11, 229−249.
(4) (a) Lee, S. H.; Gupta, M. K.; Bang, J. B.; Bae, H.; Sung, H. J. Adv.
Healthcare Mater. 2013, 2, 908−915. (b) Vo, C. D.; Kilcher, G.; Tirelli,
N. Macromol. Rapid Commun. 2009, 30, 299−315. (c) Lallana, E.;
Tirelli, N. Macromol. Chem. Phys. 2013, 214, 143−158. (d) Lippert, A.
R.; Van de Bittner, G. C.; Chang, C. J. Acc. Chem. Res. 2011, 44, 793−
804. (e) Schaferling, M.; Grogel, D. B.; Schreml, S. Microchim. Acta
̈
̈
2011, 174, 1−18. (f) Zhou, J.; Tsai, Y.-T.; Weng, H.; Tang, L. Free
Radical Biol. Med. 2012, 52, 218−226.
(5) (a) Napoli, A.; Valentini, M.; Tirelli, N.; Muller, M.; Hubbell, J.
̈
A. Nat. Mater. 2004, 3, 183−189. (b) Rehor, A.; Schmoekel, H.;
Tirelli, N.; Hubbell, J. A. Biomaterials 2008, 29, 1958−1966. (c) Allen,
B. L.; Johnson, J. D.; Walker, J. P. ACS Nano 2011, 5, 5263−5272.
(d) Wilson, D. S.; Dalmasso, G.; Wang, L.; Sitaraman, S. V.; Merlin,
D.; Murthy, N. Nat. Mater. 2010, 9, 923−928. (e) Shim, M. S.; Xia, Y.
Angew. Chem., Int. Ed. 2013, 52, 6926−6929. (f) Ma, N.; Li, Y.; Xu, H.;
Wang, Z.; Zhang, X. J. Am. Chem. Soc. 2010, 132, 442−443. (g) Liu, J.;
Pang, Y.; Zhu, Z.; Wang, D.; Li, C.; Huang, W.; Zhu, X.; Yan, D.
Biomacromolecules 2013, 14, 1627−1636. (h) Lee, D.; Khaja, S.;
Velasquez-Castano, J. C.; Dasari, M.; Sun, C.; Petros, J.; Taylor, W. R.;
Murthy, N. Nat. Mater. 2007, 6, 765−769. (i) Lee, Y.-D.; Lim, C.-K.;
Singh, A.; Koh, J.; Kim, J.; Kwon, I. C.; Kim, S. ACS Nano 2012, 6,
6759−6766. (j) Yu, S. S.; Koblin, R. L.; Zachman, A. L.; Perrien, D. S.;
Hofmeister, L. H.; Giorgio, T. D.; Sung, H.-J. Biomacromolecules 2011,
12, 4375−4366.
ASSOCIATED CONTENT
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S
* Supporting Information
Detailed synthetic procedures, H and 13C NMR spectra and
1
FT-IR spectrum of A1, A2, and A3; NMR spectra of the model
molecules, GPC curves of polymers, more H NMR spectra of
the oxidation products. This material is available free of charge
1
AUTHOR INFORMATION
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Corresponding Authors
*Phone +86-10-62757155; Fax +86-10-62751708; e-mail
(6) Kuivila, H. G. J. Am. Chem. Soc. 1954, 76, 870−874.
(7) (a) Van de Bittner, G. C.; Bertozzi, C. R.; Chang, C. J. J. Am.
Chem. Soc. 2013, 135, 1783−1795. (b) Karton-Lifshin, N.; Segal, E.;
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dx.doi.org/10.1021/ma401656t | Macromolecules 2013, 46, 8416−8425