Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates

被引：27

作者：

Cuchelkar, Vaikunth ^{[1
]}

Kopeckova, Pavla ^{[1
,2
]}

Kopecek, Jindrich ^{[1
,2
]}

机构：

[1] Univ Utah, Dept Bioengn, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA

[2] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA

来源：

MACROMOLECULAR BIOSCIENCE | 2008年 / 8卷 / 05期

关键词：

disulfide bonds; drug delivery systems; HPMA; photosensitizers; water-soluble polymers;

D O I：

10.1002/mabi.200700240

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel polymeric delivery systems for the photosensitizer mesochlorin e(6) (Mce(6))were synthesized to overcome problems of systemic toxicity. A disulfide bond was included to allow for quick release of Mce(6) from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone once internalized in tumor tissue. The synthesized conjugates demonstrated a time-dependent reductive cleavage with an accompanying increase in the quantum yield of singlet oxygen generation on exposure to DTT. Quicker release kinetics and a higher cytotoxicity in SKOV-3 human ovarian carcinoma cells were obtained as compared to polymer conjugate with a proteolytically cleavable GFLG spacer. These novel conjugates hold promise as clinically relevant drug delivery systems for photodynamic therapy of cancer.

引用

页码：375 / 383

页数：9

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