Fully Protected Glycosylated Zinc (II) Phthalocyanine Shows High Uptake and Photodynamic Cytotoxicity in MCF‐7 Cancer Cells

Abstract

Phthalocyanine photosensitizers are effective in anticancer photodynamic therapy (PDT) but suffer from limited solubility, limited cellular uptake and limited selectivity for cancer cells. To improve these characteristics, we synthesized isopropylidene-protected and partially deprotected tetra β-glycosylated zinc (II) phthalocyanines and compared their uptake and accumulation kinetics, subcellular localization, in vitro photocytotoxicity and reactive oxygen species generation with those of disulfonated aluminum phthalocyanine. In MCF-7 cancer cells, one of the compounds, zinc phthalocyanine {4}, demonstrated 10-fold higher uptake, 5-fold greater PDT-induced cellular reactive oxygen species concentration and 2-fold greater phototoxicity than equimolar (9 μm) disulfonated aluminum phthalocyanine. Thus, isopropylidene-protected β-glycosylation of phthalocyanines provides a simple method of improving the efficacy of PDT.

Glycosylated Porphyrins, Phthalocyanines, and Other Porphyrinoids for Diagnostics and Therapeutics

“…323 The low biological efficacy of tetra- β -glycosylated Zn(II)Pc as compared to protected conjugate was attributed to the aggregation caused by the hydrophobic stacking between the aromatic rings of Pc and H-bonding between the free OH groups on glucose.…”

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

“…32,35 Concisely, A2780/AD cells were treated with LOGr-Pc-LHRH at Pc concentration of 2.0 µg/mL (LOGr 3.5 µg/mL) for 24 hours. The next day, the cells were rinsed with DPBS, and 100 µL of 10 µM DCFH-DA was added under dark, 30 minutes before light treatment.…”

Synthesis of Glycoconjugated Phthalonitriles for New Phthalocyanine-Based Photosensitizers

“…Alkyl bistosylates, which are widely used in synthetic organic chemistry, such as the synthesis of crown ethers, [43] acetals, [44] and macrocycles, [45] seemed to be promising starting materials. 1,5-Pentanediyl bistosylate (26), 1,4-butanediyl bistosylate (27), 1,3-propanediyl bistosylate (28), and 1,2-ethanediyl bistosylate (29) were obtained by reactions of the corresponding diols with p-toluenesulfonyl chloride in dry pyridine. [44] Subsequently, all four alkyl spacers of different lengths were successfully introduced to galactose 2, mannofuranose 9, and glucofuranoside 10 8 G. Crucius using bistosylates 26-29 as starting materials.…”

“…[14][15][16] In addition, these carbohydrate residues enhance the solvation properties of the photosensitizer to ensure more effective photocytotoxic activity. [17][18][19][20][21][22][23][24][25][26][27][28] In previous studies we have synthesized and fully characterized a series of peripheral glycosylated and glycoconjugated zinc (II) phthalocyanines bearing galactose, glucose, mannose, maltose, or cellobiose residues at the macrocyclic skeleton. Connection of the glycosides with the aromatic system was carried out via an oxygen or sulfur atom at C-1 or C-6 of the appropriated carbohydrate using nucleophilic aromatic displacement reactions at the phthalonitrile stages.…”