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Synthesis and Biological Evaluation of Disulfide‐Linked HPMA Copolymer‐Mesochlorin e 6 Conjugates
Author(s) -
Cuchelkar Vaikunth,
Kopečková Pavla,
Kopeček Jindřich
Publication year - 2008
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200700240
Subject(s) - methacrylamide , photosensitizer , singlet oxygen , chemistry , conjugate , copolymer , cytotoxicity , drug delivery , photodynamic therapy , combinatorial chemistry , raft , polymer , polymer chemistry , biophysics , photochemistry , in vitro , organic chemistry , biochemistry , oxygen , mathematical analysis , acrylamide , mathematics , biology
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.