TARGETABLE PHOTOACTIVATABLE POLYMERIC DRUGS

被引：11

作者：

KOPECEK, J

RIHOVA, B

KRINICK, NL

机构：

[1] Department of Bioengineering, University of Utah, Salt Lake City, UT

[2] Institute of Microbiology CSAS, Prague

来源：

JOURNAL OF CONTROLLED RELEASE | 1991年 / 16卷 / 1-2期

关键词：

N-(2-HYDROXYPROPYL) METHACRYLAMIDE COPOLYMERS; TARGETABLE POLYMERIC DRUG CARRIERS; PHOTODYNAMIC THERAPY; CHLORIN E6;

D O I：

10.1016/0168-3659(91)90037-E

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The design of targetable polymeric photoactivatable drugs based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers is described. Two types of conjugates have been synthesized: (a) HPMA copolymer-galactosamine-chlorin e6 conjugates; and (b) HPMA copolymer-anti-Thy 1.2 antibody-chlorin e6 conjugates. Their photodynamic activity was evaluated in vitro. The conjugate containing galactosamine as the targeting moiety was tested on a human hepatoma cell line (PLC/PRF/5; Alexander cells) containing the asialoglycoprotein receptor. It was shown that the targetable conjugate was more active in vitro when compared with an HPMA copolymer-chlorin e6 conjugate. The photodynamic activity of two HPMA copolymer-anti-Thy 1.2 antibody-chlorin e6 conjugates was evaluated towards mouse splenocytes in vitro. They differ in the method of antibody binding. One contained anti-Thy 1.2 antibodies bound via N-epsilon-amino groups of lysine residues, the other contained anti-Thy 1.2 antibodies bound via oxidized carbohydrate groups. Both targetable conjugates were more biologically active when compared to a nontargetable HPMA copolymer-chlorin e6 conjugate. The conjugate which contained anti-Thy 1.2 antibodies bound via carbohydrate groups was the most active both in its photodynamic effect on the viability of splenocytes and the suppression of the primary antibody response of mouse splenocytes towards sheep red blood cells in vitro.

引用

页码：137 / 143

页数：7

共 20 条

[1] Kopecek, Biodegradation of polymers for biomedical use, IUPAC Macromolecules, pp. 305-320, (1982)
[2] Kopecek, Duncan, Targetable polymeric drugs, Journal of Controlled Release, 6, pp. 315-327, (1987)
[3] Kopecek, Duncan, Poly[N(2-hydroxypropyl)methacrylamide macromolecules as drug carrier systems, Polymers in Controlled Drug Delivery, pp. 152-170, (1987)
[4] Duncan, Hume, Kopeckova, Ulbrich, Strohalm, Kopecek, Anticancer agents coupled to N-(2-hydroxypropyO-methacrylamide copolymers. 3. Evaluation of adriamycin conjugates against mouse leukemia L1210 in vivo, J. Controlled Release, 10, pp. 51-63, (1989)
[5] Duncan, Kopeckova, Strohalm, Hume, Lloyd, Kopecek, Anticancer agents coupled to N-(2-hydroxypropyl)methacrylarnide copolymers. 2. Evaluation of daunomycin conjugates in vivo against L1210 leukemia, Br. J. Cancer, 57, pp. 147-156, (1988)
[6] Rihova, Kopeckova, Strohalm, Rossmann, Vetvicka, Kopecek, Antibody directed affinity therapy applied to the immune system: in vivo effectiveness and limited toxicity of daunomycin conjugates to HPMA copolymers and targeting antibody, Clin. Immunol. Immunopathol., 46, pp. 100-114, (1988)
[7] Spikes, Photosensitization, The Science of Photobiology, pp. 87-112, (1977)
[8] Straight, Spikes, Photosensitized oxidation of biomolecules, 4, pp. 91-143, (1985)
[9] Ash, Brown, Photodynamic therapy-achievements and prospects, Br. J. Cancer, 60, pp. 151-152, (1989)
[10] Henderson, Dougherty, Malone, Studies on the mechanism of tumor destruction by photoradiation therapy, Porphyrin Localization and Treatment of Tumors, (1984)

← 1 2 →