Evaluation of a Robust, Biodegradable Dendrimer
Bioconjugate Chem., Vol. 21, No. 4, 2010 773
(24) Lim, J., Guo, Y., Rostollan, C. L., Stanfield, J., Hsieh, J. T.,
Sun, X. K., and Simanek, E. E. (2008) The role of the size and
number of polyethylene glycol chains in the biodistribution and
tumor localization of triazine dendrimers. Mol. Pharmaceut. 5,
540–547.
(25) Esfand, R., and Tomalia, D. (2001) Poly(amidoamine)
(PAMAM) dendrimers: from biomimicry to drug delivery and
biomedical applications. Drug DiscoVery Today 6, 427–436.
(26) Khandare, J. J., Jayant, S., Singh, A., Chandna, P., Wang,
Y., Vorsa, N., and Minko, T. (2006) Dendrimer versus linear
conjugate: Influence of polymeric architecture on the delivery
and anticancer effect of paclitaxel. Bioconjugate Chem. 17, 1464–
1472.
(38) Goodwin, a. P., Lam, S. S., and Fre´chet, J. M. J. (2007) Rapid,
efficient synthesis of heterobifunctional biodegradable dendrim-
ers. J. Am. Chem. Soc. 129, 6994–6995.
(39) Guillaudeu, S. J., Fox, M. E., Haidar, Y. M., Dy, E. E., Szoka,
F. C., and Fre´chet, J. M. J. (2008) PEGylated dendrimers with
core functionality for biological applications. Bioconjugate Chem.
19, 461–469.
(40) King, H. D., Yurgaitis, D., Willner, D., Firestone, R. A., Yang,
M. B., Lasch, S. J., Hellstrom, K. E., and Trail, P. A. (1999)
Monoclonal antibody conjugates of doxorubicin prepared with
branched linkers: A novel method for increasing the potency of
doxorubicin immunoconjugates. Bioconjugate Chem. 10, 279–
288.
(27) Kono, K., Kojima, C., Hayashi, N., Nishisaka, E., Kiura, K.,
Wataral, S., and Harada, A. (2008) Preparation and cytotoxic
activity of poly(ethylene glycol)-modified poly(amidoamine)
dendrimers bearing adriamycin. Biomaterials 29, 1664–1675.
(28) Bhadra, D., Bhadra, S., Jain, S., and Jain, N. K. (2003) A
PEGylated dendritic nanoparticulate carrier of fluorouracil. Int.
J. Pharm. 257, 111–124.
(29) Patri, A. K., Myc, A., Beals, J., Thomas, T. P., Bander, N. H.,
and Baker, J. R. (2004) Synthesis and in vitro testing of J591
antibody-dendrimer conjugates for targeted prostate cancer
therapy. Bioconjugate Chem. 15, 1174–1181.
(30) Malik, N., Evagorou, E. G., and Duncan, R. (1999) Dendrimer-
platinate: a novel approach to cancer chemotherapy. Anti-Cancer
Drugs 10, 767–776.
(31) Kaminskas, L. M., Kelly, B. D., McLeod, V. M., Boyd, B. J.,
Krippner, G. Y., Williams, E. D., and Porter, C. J. H. (2009)
Pharmacokinetics and tumor disposition of PEGylated, meth-
otrexate conjugated poly-L-lysine dendrimers. Mol. Pharmaceut.
6, 1190–1204.
(32) Kaneshiro, T. L., Wang, X., and Lu, Z. R. (2007) Synthesis,
characterization, and gene delivery of poly-L-lysine octa(3-
aminopropyl)silsesquioxane dendrimers: nanoglobular drug car-
riers with precisely defined molecular architectures. Mol. Phar-
maceut. 4, 759–768.
(33) Okuda, T., Kawakami, S., Akimoto, N., Niidome, T., Ya-
mashita, F., and Hashida, M. (2006) PEGylated lysine dendrimers
for tumor-selective targeting after intravenous injection in tumor-
bearing mice. J. Controlled Release 116, 330–336.
(34) Grinstaff, M. W. (2002) Biodendrimers: New polymeric
biomaterials for tissues engineering. Chem.sEur. J. 8, 2838–
2846.
(35) Malik, N., Wiwattanapatapee, R., Klopsch, R., Lorenz, K.,
Frey, H., Weener, J. W., Meijer, E. W., Paulus, W., and Duncan,
R. (2000) Dendrimers: Relationship between structure and
biocompatibility in vitro, and preliminary studies on the biodis-
tribution of I-125-labelled polyamidoamine dendrimers in vivo
(vol 65, pg 133, 2000). J. Controlled Release 68, 299–302.
(36) Gillies, E. R., Dy, E., Fre´chet, J. M. J., and Szoka, F. C. (2005)
Biological evaluation of polyester dendrimer: Poly(ethylene
oxide) “Bow-Tie” hybrids with tunable molecular weight and
architecture. Mol. Pharmaceut. 2, 129–138.
(37) Gillies, E. R., and Fre´chet, J. M. J. (2002) Designing
macromolecules for therapeutic applications: Polyester den-
drimer-poly(ethylene oxide) “bow-tie” hybrids with tunable
molecular weight and architecture. J. Am. Chem. Soc. 124,
14137–14146.
(41) Fox, M. E., Guillaudeu, S., Fre´chet, J. M. J., Jerger, K.,
Macaraeg, N., and Szoka, F. C. (2009) Synthesis and in vivo
antitumor efficacy of PEGylated poly(l-lysine) dendrimer-camp-
tothecin conjugates. Mol. Pharmaceut. 6, 1562–1572.
(42) Gabbay, E. J., Grier, D., Fingerle, R. E., Reimer, R., Levy,
R., Pearce, S. W., and Wilson, W. D. (1976) Interaction
specificity of anthracyclines with deoxyribonucleic-acid. Bio-
chemistry 15, 2062–2070.
(43) Lee, C. C., Cramer, A. T., Szoka, F. C., and Fre´chet, J. M. J.
(2006) An intramolecular cyclization reaction is responsible for
the in vivo inefficacy and apparent pH insensitive hydrolysis
kinetics of hydrazone carboxylate derivatives of doxorubicin.
Bioconjugate Chem. 17, 1364–1368.
(44) Martinez, J., and Bodanszky, M. (1978) Side reactions in
peptide-synthesis.9. suppression of the formation of aminosuc-
cinyl peptides with additives. Int. J. Pept. Protein Res. 12, 277–
283.
(45) Tekade, R. K., Kumar, P. V., and Jain, N. K. (2009)
Dendrimers in oncology: an expanding horizon. Chem. ReV. 109,
49–87.
(46) Kaminskas, L. M., Boyd, B. J., Karellas, P., Krippner, G. Y.,
Lessene, R., Kelly, B., and Porter, C. J. H. (2008) The impact
of molecular weight and PEG chain length on the systemic
pharmacokinetics of PEGylated poly L-lysine dendrimers. Mol.
Pharmaceut. 5, 449–463.
(47) Denkewalter. (1982) U.S. Patent, 4, 360,646.
(48) Seymour, L. W., Duncan, R., Strohalm, J., and Kopecek, J.
(1987) Effect of molecular-weight (Mw) of n-(2-hydroxypropyl)
methacrylamide copolymers on body distribution and rate of
excretion after subcutaneous, intraperitoneal, and intravenous
administration to rats. J. Biomed. Mater. Res. 21, 1341–1358.
(49) Kratz, F., Warnecke, A., Schmid, B., Chung, D. E., and Gitzel,
M. (2006) Prodrugs of anthracyclines in cancer chemotherapy.
Curr. Med. Chem. 13, 477–523.
(50) Bae, Y., Nishiyama, N., Fukushima, S., Koyama, H., Yasuhiro,
M., and Kataoka, K. (2005) Preparation and biological charac-
terization of polymeric micelle drug carriers with intracellular
pH-triggered drug release property: Tumor permeability, con-
trolled subcellular drug distribution, and enhanced in vivo
antitumor efficacy. Bioconjugate Chem. 16, 122–130.
(51) Ulbrich, K., Etrych, T., Chytil, P., Jelinkova, M., and Rihova,
B. (2003) HPMA copolymers with pH-controlled release of
doxorubicin - In vitro cytotoxicity and in vivo antitumor activity.
J. Controlled Release 87, 33–47.
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