ACS Medicinal Chemistry Letters
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methacryloyloxyethyl phosphorylcholine polymers. J Biomed Mater
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determined to be uptake efficiency and endosomal entrapment.
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From all tested cell lines thus far, only A549 cells are exhibitꢀ
ing endosomal entrapment of the FITCꢀCOLꢀCPP carrier that
significantly lowers the potency of the drug expressed as IC50.
The endosomal entrapment of FITCꢀCOLꢀCPP was not obꢀ
served in other tested cell lines, thus it seems COLꢀCPP has a
potential to be an effective drug carrier for PTX. In addition,
the potential ease of COLꢀCPP modification to carry a variety
of molecular cargo by simply exchanging one (or several)
amino acids to lysine and employ it as convenient modificaꢀ
tion site makes our method suitable for a range of applications.
(6) Ma, P.; Mumper, R.J.; Paclitaxel NanoꢀDelivery Systems: A
Comprehensive Review. J Nanomed. Nanotechnol. 2013, 4, 1000164.
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J.R.; Spasojevic, I.; Li, X.; Lin, C.C.; Chi, J.T.A.; Chilkoti A. A
PaclitaxelꢀLoaded Recombinant Polypeptide Nanoparticle Outperꢀ
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Full experimental details copies of NMR and MS spectra for synꢀ
thesized compounds. Procedures for solubility assays, circular
dichroism spectroscopy, cell cultures, IC50 assays, confocal miꢀ
croscopy and flow cytometry, supplemental figures (PDF)
(10) Ganesh, T. Improved biochemical strategies for targeted deꢀ
livery of taxoids, Bioorg. Med. Chem., 2007, 15, 3597ꢀ3623.
(11) Chen, C.; Zhou, J.L.; Han, X.; Song, F.; Wang, X.L.; Wang,
Y.Z. A prodrug strategy based on chitosan for efficient intracellular
anticancer drug delivery. Nanotechnology 2014, 25, 255101.
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K.; Hara, K.; Hara, K.; Iwatani, W.; Amano, T.; Nakamura, K.;
Tsuchiya, Y. Synthesis and Biological Evaluation of Water Soluble
Taxoids Bearing Sugar Moieties. Heterocycles, 2001, 54, 561ꢀ566.
(13) Duncan, R.; GacꢀBreton, S.; Keane, R.; Musila, R.; Sat, Y.N.;
Satchi, R.; Searle, F.; Polymer–drug conjugates, PDEPT and PELT:
basic principles for design and transfer from the laboratory to clinic,
J. Control. Release, 2001, 74, 135ꢀ146.
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icines for treating cancer. Trends Biotechnol., 2006, 24, 39ꢀ47.
(15) Barbucci, R. (Ed.) Integrated Biomaterials Science, Kulwer
Academic / Plenum Publishers, New York 2002
(16) McGregor, D.P. Discovering and Improving novel peptide
therapeutics. Curr. Opin. Pharm., 2008, 8, 616ꢀ619.
(17) Werle, M.; BernkopꢀSchnurch, A.; Strategies to Improve
Plasma Half Life Time of Peptide and Protein Drugs. Amino Acids,
2006, 30, 351ꢀ367.
(18) Shinde, A.; Feher, K.M.; Hu, C.; Slowinska, K. Peptide interꢀ
nalization enabled by folding: triple helical cellꢀ penetrating peptides,
Journal of Peptide Science, 2015, 21 (2), 77ꢀ83.
(19) Oh, M.; Hu, C.; Urfano, S.F.; Arostegui, A.; Slowinska, K.
Thermoresponsive Collagen/Cell Penetrating Hybrid Peptide as
Nanocarrier in TargetingꢀFree Cell Selection and Uptake. Anal.
Chem. 2016, 88, 9654−9661.
(20) Deutsch, H.M.; Glinski, J.A.; Hernandez, M.; Haugwitz, R.D.;
Narayanan, V.L.; Suffness, M.; Zalkow, L.H.; Synthesis of congeners
and prodrugs. 3. Waterꢀsoluble prodrugs of taxol with potent antiꢀ
tumor activity, J. Med. Chem., 1989, 32, 788ꢀ796.
AUTHOR INFORMATION
Corresponding Author
* katarzyna.slowinska@csulb.edu
Author Contributions
The manuscript was written through contributions of all authors. /
All authors have given approval to the final version of the manuꢀ
script.
Funding Sources
This work was funded by the National Institutes of Health
GM099594 and National Science Foundation MRI DBI0722757
(confocal microscopy). Selina F. Urfano was supported by the
National Institute of General Medical Sciences of the National
Institutes of Health under Award Numbers TL4GM118980. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes
of Health.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We acknowledge Mona Oumais and Chloe Hu for help in this
project. We are grateful to Dr. Vasanthy Narayanaswami and
Siobanth Cruz for help with immunoassays.
(21) Fu, Q.; Wang, Y.; Ma, Y.; Zhang, D.; Fallon, J.K.; Yang, X.;
Liu, D.; He, Z.; Liu, F. Programmed Hydrolysis in Designing
Paclitaxel Prodrug for Nanocarrier Assembly, Scientific Reports,
2015, 5, 12023.
(22) Gauba, V.; Hartgerink, J.D. Surprisingly High Stability of
Collagen ABC Heterotimer: Evaluation of Side Chain Charge Pairs, ,
J. Am. Chem. Soc., 2007, 129, 15034ꢀ15041.
(23)Liebmann, J.E.; Cook, J.A.; Lipschultz, C.; Teague, D.; Fisher,
J.; Mitchell, J.B. Cytotoxic studies of paclitaxel (Taxol) in human
tumour cell lines. Br J Cancer. 1993, 68, 1104ꢀ1109.
ABBREVIATIONS
PTX paclitaxel, COL collagen, CPP cell penetrating peptide, P
proline, O hydroxyproline, G glycine, K lysine, Aβ betaꢀalanine, R
arginine, FITC fluorescein, CD circular dichroism
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