New Amphiphilic Silicon(IV) Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy: Synthesis, Photophysical Properties, and in vitro Photodynamic Activities

Abstract

A novel series of silicon(IV) phthalocyanines substituted axially with one or two 1,3-bis(dimethylamino)-2-propoxy group(s) have been prepared by ligand substitution and alkoxy exchange reactions. Two dicationic and tetracationic phthalocyanines have also been prepared by methylation of two of these compounds. The nonionic phthalocyanines are essentially nonaggregated in common organic solvents and show a weak fluorescence emission, while the methylated derivatives are also nonaggregated, even in aqueous media, and exhibit a strong fluorescence emission. These new phthalocyanines, in particular the unsymmetrical and amphiphilic analogues, are highly potent against HepG2 human hepatocarcinoma cells and J774 mouse macrophage cells with IC50 values down to 0.02 microM. The photodynamic activities are related to the cellular uptake and the efficiency to generate singlet oxygen. A higher positive charge at the phthalocyanine hinders the uptake, reflected by the lower intracellular fluorescence intensity. Fluorescence microscopic studies have also revealed that the unsymmetrical phthalocyanine SiPc[C3H5(NMe2)2O](OMe) (4) has a high and selective affinity to the mitochondria of HepG2 cells.

Photodynamic activity of a glucoconjugated silicon(IV) phthalocyanine on human colon adenocarcinoma

“…20 For example, a hydrophilic SiPc tends to localize in the lysosome, 21 while BAMSiPc, an unsymmetric bisamino SiPc, is found exclusively in the mitochondria. 22 On the other hand, phthalocyanines with diffused localization, for example Pc 4, 23 have also been described. Thus, the conjugated groups are crucial for the exact subcellular localization, for it might affect the apoptotic pathway being triggered.…”

Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model

“…Preparation of BAM-SiPc BAM-SiPc was synthesized according to the procedure of Lo et al 36 For in vitro assays, a BAM-SiPc stock solution was prepared by dissolving BAM-SiPc powder in dimethylformamide (494488, Sigma-Aldrich, St. Louis, MO, US), followed by a 10-fold dilution using 0.01 M aqueous Cremophor EL (C5135, Sigma-Aldrich, St. Louis, MO, US). The stock solution was further diluted to suitable concentrations using complete RPMI-1640 medium (23400021, Invitrogen, Carlsbad, CA, US).…”

“…Among them, BAM-SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine, is one of the most potent PSs. 36 BAM-SiPc was non-toxic in the dark at concentrations as high as 4 mM; however, with illumination, it showed an IC 50 value of ,20 nM toward various cell lines. [36][37][38] The photo-cytotoxic effect of BAM-SiPc has also been studied in the tumor-bearing nude mouse model using a classical PDT protocol.…”

“…36 BAM-SiPc was non-toxic in the dark at concentrations as high as 4 mM; however, with illumination, it showed an IC 50 value of ,20 nM toward various cell lines. [36][37][38] The photo-cytotoxic effect of BAM-SiPc has also been studied in the tumor-bearing nude mouse model using a classical PDT protocol. The results showed that BAM-SiPc could significantly reduce the size of HepG2 tumors and retard the growth of HT29 tumors with no apparent hepatic or cardiac injury.…”

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

“…DPcloaded PIC micelles were prepared and tested in a solid tumor model. 28,[44][45][46] DPc-loaded micelles, approximately 50 nm in diameter, were prepared from DPc and PEG-b-PLL in a manner similar to the DP-loaded micelles. 47 Unlike DP, loading DPc into micelles shifted the absorption maximum from 685 to 630 nm, indicating possible interactions between the phthalocyanine units in the micellar core.…”