Journal of Medicinal Chemistry
Article
(8) Kim, T.; Chen, Y.; Mount, C.; Gambotz, W.; Li, X.; Pun, S.
Evaluation of Temperture-Sensitive, Indocyanine Green-Encapsulating
Micelles for Noninvasive Near-Infrared Tumor Imaging. Pharm. Res.
2
(
010, 27, 1900−1913.
AUTHOR INFORMATION
■
9) Jia, Z.; Wong, L.; Davis, T. P.; Bulmus, V. One-pot conversion of
Corresponding Author
Mailing address: H. Lee Moffitt Cancer Center & Research
Institute, Department of Cancer Imaging and Metabolism,
RAFT-generated multifunctional block copolymers of HPMA to
doxorubicin conjugated acid- and reductant-sensitive crosslinked
micelles. Biomacromolecules 2008, 9, 3106−3113.
*
(
10) Yang, X.; Grailer, J. J.; Pilla, S.; Steebe, D. A.; Gong, S. Tumor-
1
7
Targeting, pH-Responsive, and Stable Unimolecular Micelles as Drug
Nanocarriers for Targeted Cancer Therapy. Bioconjugate Chem. 2010,
Author Contributions
All authors contributed to the writing of this manuscript.
2
(
1, 496−504.
11) Li, Y.; Xio, W.; Xiao, K.; Berti, L.; Luo, J.; Tseng, H.; Fung, G.;
Lam, K. Well-definied reversible boronate crosslinked nanocarriers for
targeted drug delivery in response to acidic pH values and cis-diols.
Angew. Chem., Int. Ed. 2012, 51, 1−7.
Notes
The authors declare no competing financial interest.
(12) Cannan, R. K.; Kibrick, A. Complex Formation between
ACKNOWLEDGMENTS
■
Carboxylic Acids and Divalent Metal Cations. J. Am. Chem. Soc. 1938,
60, 2314−2320.
(13) Rios-Doria, J.; Carie, A.; Costich, T.; Burke, B.; Skaff, H.;
Panicucci, R.; Sill, K. A versatile polymer micelle drug delivery system
for encapsulation and in vivo stabilization of hydrophobic anticancer
drugs. J. Drug Delivery 2012, No. 951741.
Research was funded by the Bankhead Coley Melanoma Pre-
SPORE Program (Grant 02-15066-10-03) to D.L.M., NIH/
NCI (Grant R01 CA 097360 to R.J.G. and D.L.M.; CA 68682
to J.L.S.), and Intezyne Inc. (Award No. 84-16301-01-01) to
R.J.G. for a portion of N.M.B.’s salary and polymer materials.
The authors acknowledge Professor Dean Sherry (UTSW) for
his invaluable wisdom and insight.
(14) Sun, T.-M.; Du, J.-Z.; Yao, Y.-D.; Mao, C.-Q.; Dou, S.; Huang,
S.-Y.; Zhang, P.-Z.; Leong, K.; Song, E.-W.; Wang, J. Simultaneous
delivery of siRNA and pacilitaxel via a “two-in-one” micelleplex
promotes synergistic tumor supression. ACS Nano 2011, 5, 1483−
1494.
ABBREVIATIONS USED
■
(15) Koo, H.; Huh, M.; Sun, I.-C.; Yuk, S.; Choi, K.; Kim, K.; Kwon,
IVECT, Trademarked name of Intezyne Technology’s triblock
polymer; Gd-Tx, gadolinium texaphyrin; RGD, integrin αvβ3
three amino-acid residue ligand (arginine, glycine, aspartic
acid); MC1R, melanocortin 1 receptor; MSH, melanocyte
stimulation hormone; MC3R, melanocortin 3 receptor; MC4R,
melanocortin 4 receptor; MC5R, melanocortin 5 receptor;
MC2R, melanocortin 2 receptor; XL, cross-linked; UXL, un-
cross-linked; T, targeted; UT, untargeted; TRF, time-resolved
fluorescence; SEMS, spin echo multislice; R, right; L, left; ROI,
region of interest; IACUC, institutional animal care and use
committee
I. In vivo targeted delivery of nanoparticles for theranosis. Acc. Chem.
Res. 2011, 44, 1018−1028.
(16) Tang, N.; Dy, G.; Wang, N.; Liu, C.; Hang, H.; Liang, W.
Improving Penetration in Tumors with Nanoassemblies of Phospho-
lipids and Doxorubicin. J. Natl. Cancer Inst. 2007, 99, 1004−1015.
(17) Chrastina, A.; Massey, K. A.; Schnitzer, J. E. Overcoming in vivo
barriers to targeted nanodelivery. Wiley Interdiscip. Rev.: Nanomed.
Nanobiotechnol. 2011, 3, 421−437.
(18) Kessinger, C.; Khemtong, C.; Togao, O.; Takahashi, M.; Sumer,
B.; Gao, J. In-vivo angiogenesis imaging of solid tumors by avb3-
targeted, dual-modality micellar nanoprobes. Exp. Biol. Med. 2010,
2
(
35, 957−965.
19) Poon, Z.; Lee, J.; Huang, S.; Prevost, R.; Hammond, P. Highly
REFERENCES
■
Stable, Ligand Clustered “Patchy” Micelle Nanocarriers for Systemic
Tumor Targeting. Nanomedicine 2010, 1−30.
(
1) Yokoyama, M. Clinical Applications of Polymeric Micelle Carrier
Systems in Chemotherapy and Image Diagnosis of Solid Tumors. J
Exp Clin Med 2011, 3, 151−158.
2) Oerlemans, C.; Bult, W.; Bos, M.; Storm, G.; Nijsen, J. F. W.;
Hennink, W. E. Polymeric micelles in Anticancer Therapy: Targeting,
Imaging, and Triggered Release. Pharm. Res. 2010, 27, 2569−2589.
3) Kedar, U.; Phutane, P.; Shidhaye, S.; Kadam, V. Advances in
Polymeric Micelles for Drug Delivery and Tumor Targeting.
Nanomedicine 2010, 6, 714−729.
4) Kim, S.; Shi, Y.; Kim, J. Y.; K., P.; Chen, J.-X. Overcoming the
barriers in micellar drug delivery: Loading efficiency, in vivo stability,
and micelle−cell interaction. Expert Opin. Drug Delivery 2010, 7, 49−
(20) Lee, H.; Fonge, H.; Hoang, B.; Reilly, R.; Allen, C. The Effects
of Particle Size and Molecular Targeting on teh Intratumoral and
Suncellular Distribution of Polymeric Nanoparticles. Mol. Pharmaceu-
tics 2010, 7, 1195−1208.
(
(21) Hu, J.; Qian, Y.; Wang, X.; Liu, W.; Liu, S. Drug-Loaded and
(
Superparamagnetic Iron Oxide Nanoparticle Surface-Embedded
Amphiphilic Block Copolymer Micelles for Integrated Chemo-
therapeutic Drug Delivery and MR Imaging. Langmuir 2012, 28,
(
2
(
073−2082.
22) Liu, T.; Liu, X.; Qian, Y.; Hu, X.; Liu, S. Multifunctional pH-
Disintegrable micelle nanoparticles of asymmetrically functionalized
beta-cyclodextrin-based star copolymer covalently conjugated with
doxorubicin and DOTA-Gd moieties. Biomaterials 2012, 33, 2521−
62.
(
5) Shiraishi, K.; Kawano, K.; Maitani, Y.; Yokoyama, M. Polyion
Complex Micele MRI Contrast Agents from Poly (ethylene glycol)-b-
poly(L-lysine) Block Copolymers having Gd-DOTA; Preparations and
their Control of T1 Relaxitivities and Blood Circulation Character-
istics. J. Controlled Release 2010, 1−8.
2
(
531.
23) Xiong, X.-B.; Lavasanifar, A. Traceable Multifunctional Micellar
nanocarriers for Cancer-Targeted Co-delivery of MDR-1 siRNA and
Doxorubicin. ACS Nano 2011, 5, 5202−5213.
(
6) Li, J.; Huo, M.; Wang, J.; Zhou, J.; Mohammas, J.; Zhang, Y.;
(24) Yang, R.; Meng, F.; Ma, S.; Huang, F.; Liu, H.; Zhong, Z.
Zhu, Q.; Waddad, A.; Zhang, Q. Redox-sensitive micelles self-
assembled from amphiphilic hyaluronic acid-deoxycholic acid con-
jugates for targeted intracellular delivery of paclitaxel. Biomaterials
012, 33, 2310−2320.
7) Lee, H.; Hoang, B.; Fonge, H.; Reilly, R.; Allen, C. In-Vivo
Distribution of Polymeric Nanoparticles at the Whole Body, Tumor
and Cellular Levels. Pharm. Res. 2010, 27, 2343−2355.
Galactose-decorated cross-linked biodegradable poly9ethylene glycol)-
b-poly(E-caprolactone) block copolymer micelles for enhanced
hepatoma-targeting delivery of paclitaxel. Biomacromolecules 2011,
12, 3047−3055.
(25) Siegrist, W.; Solca, F.; Stutz, S.; Giuffre, L.; Carrel, S.; Girard, J.;
Eberle, A. N. Characterization of receptors for alpha-melanocyte-
2
(
6
337
dx.doi.org/10.1021/jm4005576 | J. Med. Chem. 2013, 56, 6330−6338