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

Macromolecular Bioscience
Vaikunth CuchelkarJ Kopecek

Abstract

Novel polymeric delivery systems for the photosensitizer mesochlorin e6 (Mce6) were synthesized to overcome problems of systemic toxicity. A disulfide bond was included to allow for quick release of Mce6 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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Citations

Sep 13, 2011·Biomacromolecules·Fuxing ZhanZhiyuan Zhong
Jun 26, 2009·Journal of the American Chemical Society·Jingyi ChenIwao Ojima
Sep 5, 2008·Molecular Pharmaceutics·Vaikunth CuchelkarJindrich Kopecek
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Apr 27, 2017·Macromolecular Bioscience·Claudia Battistella, Harm-Anton Klok
Aug 15, 2017·Macromolecular Bioscience·Petr ChytilKarel Ulbrich
Oct 28, 2016·Bioengineering & Translational Medicine·Quanyou Feng, Rong Tong

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