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Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
b
CREST, Japan Science and Technology Corporation, Japan
c
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
d
Department of Clinical Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8655, Japan
Received 15 April 2003; accepted 27 May 2003
Abstract
Photosensitizers play a crucial role in the photodynamic therapy (PDT) of cancer. In this study, a third-generation aryl ether
dendrimer porphyrin with 32 primary amine groups on the periphery, [NH2CH2CH2NHCO]32DPZn, and pH-sensitive, polyion
complex micelles (PIC) composed of the porphyrin dendrimer and PEG-b-poly(aspartic acid), were evaluated as new
photosensitizers (PSs) for PDT in the Lewis Lung Carcinoma (LLC) cell line. The preliminary photophysical characteristics of
[NH2CH2CH2NHCO]32DPZn and the corresponding micelles were investigated. Electrostatic assembly resulted in a red-shift of
the Soret peak of the porphyrin core and the enhanced fluorescence. Compared to the dendrimer porphyrin
[NH2CH2CH2NHCO]32DPZn, relatively low cellular uptake of dendrimer porphyrin [NH2CH2CH2NHCO]32DPZn
incorporated in the PIC micelle was observed, yet the latter exhibited enhanced photodynamic efficacy on the LLC cell
line. Importantly, the use of PIC micelles as a delivery system reduced the dark toxicity of the cationic dendrimer porphyrin,
probably due to the biocompatible PEG shell of the micelles.
D 2003 Elsevier B.V. All rights reserved.
Keywords: Photodynamic therapy; Photosensitizer; Dendrimer porphyrin; Polyion complex micelle; Block copolymer
1. Introduction
$
Presented at 11th International Symposium on Recent
Advances in Drug Delivery Systems and CRS Winter Symposium,
Salt Lake City, UT, March 3 6, 2003.
* Corresponding author. Department of Materials Science and
Engineering, Graduate School of Engineering, The University of
Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Tel.:
+81-3-5841-7138; fax: +81-3-5841-7139.
E-mail address: kataoka@bmw.t.u-tokyo.ac.jp (K. Kataoka).
0168-3659/$ - see front matter D 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jconrel.2003.05.002
To create new photosensitizers (PSs) or their formulation plays a crucial role in the development of
photodynamic therapy (PDT). Ideal PSs should possess such characteristics as selectivity to solid tumor
tissue, and higher photocytotoxicity with lower cytotoxicity under dark conditions [1,2]. PDT of cancer
involves the systemic administration of photosensi-
142
143
144
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147
charge than normal cells resulting from overexpression of polysialic acid residues [32].
3.4. In vitro photodynamic effect and dark toxicity of
dendrimer and the micelles
148
(h)
PIX
DPZn
Micelle
4
12
4.26
1.67
0.403
0.327
0.0289
0.0275
4. Conclusion
In conclusion, nanocarriers consisting of polyion
complex micelles, composed of PEG-b-P(Asp)
and the nano-scaled dendrimer porphyrin
[NH2CH2CH2NHCO]32DPZn, could effectively deliver dendrimer porphyrin photosensitizers into
cancer cells and produce enhanced photodynamic
efficacy, over cationic dendrimer porphyrin and
PIX. Importantly, the PIC micelle formulation
exhibited no dark toxicity within the concentration
used. It is expected that this promising nanocarrier
of PIC micelles can be practical for encapsulation
of other ionic photosensitizers, especially for
phthalocyanine derivatives, typical second-generation photosensitizers.
[8]
[9]
[10]
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[12]
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Acknowledgements
This work was supported by Core Research for
Evolutional Science and Technology (CREST), Japan
Science and Technology (JST), and by a Grant-in-aid
for Scientific Research, as well as by Special
Coordination Funds for Promoting Science and
Technology, Ministry of Education, Culture, Sports,
Science and Technology, Japan (MEXT).
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