794518-55-1Relevant academic research and scientific papers
A carboxylated Zn-phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide
Tabassum, Shatera,Sheikh, Abdullah M.,Yano, Shozo,Ikeue, Takafumi,Handa, Makoto,Nagai, Atsushi
, p. 463 - 476 (2015)
Amyloid β (Aβ), a 39-42 amino acid peptide derived from amyloid precursor protein, is deposited as fibrils in Alzheimer's disease brains, and is considered to play a major role in the pathogenesis of the disease. We have investigated the effects of a water-soluble Zn-phthalocyanine, ZnPc (COONa)8, a macrocyclic compound with near-infrared optical properties, on Aβ fibril formation in vitro. A thioflavin T fluorescence assay showed that ZnPc(COONa)8 significantly inhibited Aβ fibril formation, increasing the lag time and dose-dependently decreasing the plateau level of fibril formation. Moreover, it destabilized pre-formed Aβ fibrils, resulting in an increase in low-molecular-weight species. After fibril formation in the presence of ZnPc(COONa)8, immunoprecipitation of Aβ1-42 using Aβ-specific antibody followed by near-infrared scanning demonstrated binding of ZnPc(COONa)8 to Aβ1-42. A study using the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid showed that ZnPc(COONa)8decreased the hydrophobicity during Aβ1-42 fibril formation. CD spectroscopy showed an increase in the α helix structure and a decrease in the b sheet structure of Aβ1-40 in fibril-forming buffer containing ZnPc (COONa)8. SDS/PAGE and a dot-blot immunoassay showed that ZnPc (COONa)8 delayed the disappearance of low-molecular-weight species and the appearance of higher-molecular-weight oligomeric species of Aβ1-42. A cell viability assay showed that ZnPc(COONa)8 was not toxic to a neuronal cell line (A1), but instead protected A1 cells against Aβ1-42-induced toxicity. Overall, our results indicate that ZnPc(COONa)8 binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation.
Synthesis and in vitro photodynamic activity of new hexadeca-carboxy phthalocyanines
Choi, Chi-Fung,Tsang, Po-Ting,Huang, Jian-Dong,Chan, Elaine Y. M.,Ko, Wing-Hung,Fong, Wing-Ping,Ng, Dennis K. P.
, p. 2236 - 2237 (2004)
Two new hexadeca-carboxy phthalocyanines have been synthesised and evaluated for their photodynamic activities; the zinc(II) analogue exhibits a high class-A scavenger-receptor mediated photocytotoxicity towards the J774 marine macrophage cell line.
Cationic Versus Anionic Phthalocyanines for Photodynamic Therapy: What a Difference the Charge Makes
Kollar, Jan,Machacek, Miloslav,Halaskova, Marie,Lenco, Juraj,Kucera, Radim,Demuth, Jiri,Rohlickova, Monika,Hasonova, Katerina,Miletin, Miroslav,Novakova, Veronika,Zimcik, Petr
, p. 7616 - 7632 (2020)
The literature reports on cationic and anionic phthalocyanines (Pcs) for photodynamic therapy suggest systematically significant differences in activity. In this work, ten different zinc(II) Pcs with carboxylate functions or quaternary nitrogens (hydrophilic anionic, hydrophilic cationic, amphiphilic anionic, and amphiphilic cationic) were investigated, with the aim of revealing reasons for such differences. In vitro assays on HeLa, MCF-7, and HCT-116 cells confirmed higher photoactivity for cationic Pcs (EC50 ～3-50 nM) than for anionic Pcs (EC50 ～0.3-10 μM), the latter being additionally significantly more active in serum-free medium. The environmental pH, binding to serum proteins, interaction with biomembranes, differences in subcellular localization, and relocalization after irradiation were found to be the main factors contributing to the generally lower photoactivity of anionic Pcs than that of the cationic derivatives. This result is not limited only to the presented derivatives and should be considered in the design of novel photosensitizers.
Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines
Liu, Wei,Jensen, Timothy J.,Fronczek, Frank R.,Hammer, Robert P.,Smith, Kevin M.,Vicente, M. Gra?a H.
, p. 1033 - 1041 (2005)
Water-soluble phthalocyanines are promising photosensitizers for application in cancer therapy and in the photoinactivation of viruses. The water-soluble zinc(II) phthalocyanines 5 and 6 were synthesized by converting the corresponding ester derivative 4 into the sodium carboxylate and carboxylic acid species. Compound 5 can be solubilized in water as a monomeric species, as demonstrated by UV/vis and fluorescence spectroscopy. These compounds were characterized by analytical and spectroscopic methods and, in the case of 4, by X-ray crystallography. The water-soluble phthalocyanines were found to have low dark cytotoxicity toward V79 hamster fibroblasts and human HEp2 cells, to be phototoxic at low light and drug doses, to be taken up by cells in culture, and to localize intracellularly, mainly in the cell lysosomes. Conjugation of the anionic phthalocyanines with positively charged LipoGen liposomes resulted in effective delivery of these compounds into the nuclei of cells. It is concluded that these highly water-soluble phthalocyanines are promising sensitizers for the photodynamic therapy of tumors.
Monomer zinc phthalocyanine/upconversion nanoparticle coated with hyaluronic acid crosslinked gel as NIR light-activated drug for: In vitro photodynamic therapy
Zhou, Lin,Chen, Enyi,Jin, Weiwei,Wang, Yue,Zhou, Jiahong,Wei, Shaohua
, p. 15170 - 15179 (2016/10/11)
Carboxyl group modified zinc phthalocyanines (ZnPc) are classic and widely used photosensitizers (PSs) in upconversion nanoparticles (UCNPs) mediated photodynamic therapy (PDT) for tumor treatment. To improve the PDT activity of the complex system of ZnPc and UCNPs, many UCNPs with high red emission intensity were design and prepared. ZnPc-(COOH)4 tends to aggregate both in water and under physiological conditions, which can sharply decrease its PDT activity. Therefore, choosing monomeric COOH groups modified ZnPc as PSs is an alternative way to improve their activity. In this manuscript, three zinc(ii) phthalocyanines, substituted with 4 (ZnPc-(COOH)4), 8 (ZnPc-(COOH)8) and 16 (ZnPc-(COOH)16) COOH groups, were synthesized. A comparison of the results indicated that ZnPc-(COOH)16 existed in its monomeric form under physiological conditions because of its large substituents. Moreover, ZnPc-(COOH)16 showed superior singlet oxygen (1O2) generation ability when compared to ZnPc-(COOH)4 and ZnPc-(COOH)8. Therefore, we chose ZnPc-(COOH)16 as PSs for absorption on the surface of the UCNPs. Then, they were encapsulated by crosslinked methacrylated hyaluronic acid (m-HA), which provides active tumor accumulation ability by binding its overexpressed receptors on the surface of cancer cells. The resulting nanoparticles can be effectively taken up by cancer cells and shows strong near-infrared (NIR) light triggered PDT in vitro.
A soft supramolecular carrier with enhanced singlet oxygen photosensitizing properties
Voskuhl, Jens,Kauscher, Ulrike,Gruener, Malte,Frisch, Hendrik,Wibbeling, Birgit,Strassert, Cristian A.,Ravoo, Bart Jan
, p. 2453 - 2457 (2013/05/21)
Herein we report the self-assembly of a supramolecular singlet oxygen photosensitizing system from an adamantane-functionalized, hexaanionic water-soluble zinc(ii) phthalocyanine (PC) and β-cyclodextrin vesicles (CDV). Characterisation of the designed PC, which was synthesized by an asymmetric statistical condensation, was carried out by several analytical techniques such as MALDI-HRMS, NMR, IR, UV/vis as well as steady state and time resolved fluorescence spectroscopy. The influence of the docking of the PC to the CDVs on the PC photoluminescence as well as on the singlet oxygen photoproduction quantum yields was investigated. The results indicate that the host-guest interaction of the photosensitizer and the CDVs significantly prevents the formation of inactive aggregates, and enhances the photosensitizing ability of the PC. The supramolecular assembly constitutes a biocompatible photoactive platform for the design of phototherapeutic agents.
