Collect. Czech. Chem. Commun. 1993, 58, 2321-2336

Synthesis and Photoproperties of a Substituted Zinc(II) Phthalocyanine-N-(2-hydroxypropyl)methacrylamide Copolymer Conjugate

Zhong-wei Gua, John D. Spikesb, Pavla Kopečkováa and Jindřich Kopečeka

a Department of Bioengineering, 2480 MEB, University of Utah, Salt Lake City, Utah 84112, U.S.A.
b Department of Biology, University of Utah, Salt Lake City, Utah 84112, U.S.A.


In cancer photodynamic therapy (PDT), improved efficiency of photosensitizer delivery to tumors may be obtained by binding them to targetable water soluble polymeric carriers. However, attachment of photosensitizers to Macromolecular carriers may alter their spectral and photosensitizing properties. In this study, a new monosubstituted phthalocyanine derivative, N-glycyl zinc(II) 4,9,16,23-tetraaminophthalocyanine (G-TAPC-Zn) was synthesized by the reaction of zinc(II) 4,9,16,23-tetraaminophthalocyanine (TAPC-Zn) with N-tert-butoxycarbonyl-glycine N'-hydroxybenzotriazole ester followed by deprotection of the tert-butoxycarbonyl (BOC) group. G-TAPC-Zn contains an aliphatic amino group suitable for attachment to water soluble polymeric carriers. By aminolysis of a polymeric precursor, an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer containing oligopeptide (GFLG) side-chains terminated in p-nitrophenyl ester groups, with G-TAPC-Zn a polymeric derivative of the latter (P-GFLGG-TAPC-Zn) was synthesized. Spectral data indicated that in aqueous solutions P-GFLGG-TAPC-Zn formed aggregates. The degree of aggregation decreased with increasing concentration of detergents or organic solvents in buffer solutions. Consequently, the release of the drug from carrier catalyzed by thiol proteinases, papain or cathepsin B, took place only in the presence of detergents or organic solvents, i.e., under conditions with a lower probability of aggregate formation. Binding of G-TAPC-Zn to HPMA copolymers decreased the quantum yield of singlet oxygen generation from 0.24 to 0.063 and significantly increased its resistance to photobleaching.