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Synthesis and Biological Evaluation of Disulfide-Linked HPMA Copolymer-Mesochlorin e6 Conjugates

✍ Scribed by Vaikunth Cuchelkar; Pavla Kopečková; Jindřich Kopeček

Book ID
102472932
Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
186 KB
Volume
8
Category
Article
ISSN
1616-5187

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✦ Synopsis

Abstract

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.

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