Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates.
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.
Cuchelkar
Vaikunth
V
Department of Bioengineering, Center for Controlled Chemical Delivery, 20 S 2030 E, Rm# 205, Biopolymers Research Building, University of Utah, Salt Lake City, UT 84112, USA.
Kopecková
Pavla
P
Kopecek
Jindrich
J
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis*; D016923:Cell Death; D045744:Cell Line, Tumor; D004220:Disulfides; D016503:Drug Delivery Systems; D006801:Humans; D008652:Mesoporphyrins / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents
D000970:Antineoplastic Agents; D004220:Disulfides; D008652:Mesoporphyrins; D008689:Methacrylates; D017319:Photosensitizing Agents; C088297:meso-chlorin e(6) monoethylene diamine; C032802:hydroxypropyl methacrylate