Journal of the American Chemical Society
Article
(16) Oishi, M.; Nagasaki, Y.; Itaka, K.; Nishiyama, N.; Kataoka, K. J.
Am. Chem. Soc. 2005, 127, 1624−1625.
ASSOCIATED CONTENT
* Supporting Information
Full experimental details and characterization for all com-
pounds. This material is available free of charge via the Internet
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S
(17) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in
Organic Synthesis; 4th ed.; Wiley: New York, 2007.
(18) Perkins, W. E.; Bianchi, R. G.; Tremont, S. J.; Collins, P. W.;
Casler, J. J.; Fenton, R. L.; Wagner, G. M.; McGrath, M. P.;
Stolzenbach, J. C.; Kowalski, D. L.; Gasiecki, A. F.; Forester, D.; Jones,
P. H. J. Pharmacol. Exp. Ther. 1994, 269, 151−156.
AUTHOR INFORMATION
Corresponding Author
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(19) Tremont, S. J.; Collins, P. W.; Perkins, W. E.; Fenton, R. L.;
Forster, D.; McGrath, M. P.; Wagner, G. M.; Gasiecki, A. F.; Bianchi,
R. G.; Casler, J. J.; Ponte, C. M.; Stolzenbach, J. C.; Jones, P. H.; Gard,
J. K.; Wise, W. B. J. Med. Chem. 1993, 36, 3087−3097.
(20) Davis, M. E.; Chen, Z.; Shin, D. M. Nat. Rev. Drug Discovery
2008, 7, 771−782.
Notes
The authors declare the following competing financial
interest(s): The research reported in this paper received partial
financial support from a venture capital-backed company that
Prof. Joseph M. DeSimone cofounded, Liquidia Technologies
and has personal financial interests in Liquidia Technologies.
(21) Dong, X.; Mattingly, C. A.; Tseng, M. T.; Cho, M. J.; Liu, Y.;
Adams, V. R.; Mumper, R. J. Cancer Res. 2009, 69, 3918−3926.
̃
(22) Lin, L. Y.; Lee, N. S.; Zhu, J.; NystrA¶m, A. M.; Pochan, D. J.;
Dorshow, R. B.; Wooley, K. L. J. Controlled Release 2011, 152, 37−48.
(23) Wang, A. Z.; Langer, R. S.; Farokhzad, O. C. Annu. Rev. Med.
2012, 63, 185−198.
(24) Rolland, J. P.; Maynor, B. W.; Euliss, L. E.; Exner, A. E.;
Denison, G. M.; DeSimone, J. M. J. Am. Chem. Soc. 2005, 127, 10096−
10100.
ACKNOWLEDGMENTS
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The research was supported by the following; National
Institutes of Health Grants 1R01EB009565-02,
U54CA119373, and U54CA151652 (the Carolina Center of
Cancer Nanotechnology), 1DP10D006432-01 (NIH Pioneer
Award), the University Cancer Research Fund at the University
of North Carolina at Chapel Hill, the William R. Kenan
Professorship at the University of North Carolina at Chapel
Hill, and a sponsored research agreement with Liquidia
Technologies. We would also like to acknowledge Dr. Sohrab
Habibi for obtaining the high-resolution mass spectrometry
data and Dr. Marc ter Horst for helping identify the different
isomers of the gemcitabine prodrugs by NMR.
(25) Herlihy, K. P.; Nunes, J.; DeSimone, J. M. Langmuir 2008, 24,
8421−8426.
(26) Nunes, J.; Herlihy, K. P.; Mair, L.; Superfine, R.; DeSimone, J.
M. Nano Lett. 2010, 10, 1113−1119.
(27) Gratton, S. E. A.; Ropp, P. A.; Pohlhaus, P. D.; Luft, J. C.;
Madden, V. J.; Napier, M. E.; DeSimone, J. M. Proc. Natl. Acad. Sci.
U.S.A. 2008, 105, 11613−11618.
(28) Petros, R. A.; Ropp, P. A.; DeSimone, J. M. J. Am. Chem. Soc.
2008, 130, 5008−5009.
(29) Parrott, M. C.; Luft, J. C.; Byrne, D. B.; Fain, J. H.; Napier, M.
E.; DeSimone, J. M. J. Am. Chem. Soc. 2010, 132, 17928−17932.
REFERENCES
■
(1) Huttunen, K. M.; Raunio, H.; Rautio, J. Pharmacol. Rev. 2011, 63,
750−771.
(2) Bildstein, L.; Dubernet, C.; Couvreur, P. Adv. Drug Delivery Rev.
2011, 63, 3−23.
(3) Kratz, F.; Muller, I. A.; Ryppa, C.; Warnecke, A. ChemMedChem
̈
2008, 3, 20−53.
(4) Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.;
Jarvinen, T.; Savolainen, J. Nat. Rev. Drug Discovery 2008, 7, 255−270.
(5) Mellman, I.; Fuchs, R.; Helenius, A. Annu. Rev. Biochem. 1986, 55,
663−700.
(6) Gallin, J. I.; Goldstein, I. M.; Snyderman, R. E. Inflammation
Basic Principles and Clinical Correlates, 3rd ed.; Lippincott Williams &
Wilkins: Philadelphia, PA, 1999.
(7) Engin, K.; Leeper, D. B.; Cater, J. R.; Thistlethwaite, A. J.;
Tupchong, L.; McFarlane, J. D. Int. J. Hyperthermia 1995, 11, 211−
216.
(8) Di Stefano, G.; Lanza, M.; Kratz, F.; Merina, L.; Fiume, L. Eur. J.
Pharm. Sci. 2004, 23, 393−397.
(9) Patel, V. F.; Hardin, J. N.; Mastro, J. M.; Law, K. L.;
Zimmermann, J. L.; Ehlhardt, W. J.; Woodland, J. M.; Starling, J. J.
Bioconjugate Chem. 1996, 7, 497−510.
(10) Shen, W. C.; Ryser, H. J. P. Biochem. Biophys. Res. Commun.
1981, 102, 1048−1054.
(11) Shin, J.; Shum, P.; Thompson, D. H. J. Controlled Release 2003,
91, 187−200.
(12) Heffernan, M. J.; Murthy, N. Bioconjugate Chem. 2005, 16,
1340−1342.
(13) Sankaranarayanan, J.; Mahmoud, E. A.; Kim, G.; Morachis, J.
M.; Almutairi, A. ACS Nano 2010, 4, 5930−5936.
(14) Gillies, E. R.; Frechet, J. M. J. Bioconjugate Chem. 2005, 16,
361−368.
(15) Toncheva, V.; Schacht, E.; Ng, S. Y.; Barr, J.; Heller, J. J. Drug
Targeting 2003, 11, 345−353.
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dx.doi.org/10.1021/ja301710z | J. Am. Chem. Soc. 2012, 134, 7978−7982