Improved photodynamic efficacy of thiophenyl sulfonated zinc phthalocyanine loaded in lipid nano-carriers for hepatocellular carcinoma cancer cells.

The aim of the present study was to modify the structural activity of zinc(II)phthalocyanine by combining it with thiophenyl groups then loaded in lipid nano-carriers and evaluate its parameters required for the structure-activity relationship (SAR) for photodynamic therapy (PDT) of cancer. Tetra (4-Thiophenyl) sulfonated phthalocyaninatozinc(II) (PhS·SO3Na)4ZnPc 5 was synthesized and characterized by various spectroscopic methods as a test compound. Liver hepatocellular carcinoma (HepG2) cells were treated with the synthesized (PhS·SO3Na)4ZnPc 5 derivative loaded in lipid nano carriers to understand the effect of combined compound on liver cancer cells. Furthermore, HepG2 cells were irradiated by visible red light at 60 mW/cm2 for 20 min. The phototoxicity of (PhS·SO3Na)4ZnPc 5 after being formulated in both (L) and transfersomes (T) was investigated. Overall, the results indicate that combination of thiophenyl groups substitution, in particular in the structure of sulfonated zinc phthalocyanine is able to improve the photodynamic properties of ZnPc, and (PhS·SO3Na)4ZnPc 5 loaded in lipid nano-carriers can be a promising combined PDT treatment strategy for Liver hepatocellular carcinoma (HepG2) cells. The new formulation ZnPc-lipid nano-carriers will be beneficial in the upcoming clinical trials and would enhance the inhibition of tumor growth.

Abdel Fadeel D ，Al-Toukhy GM ，Elsharif AM ，Al-Jameel SS ，Mohamed HH ，Youssef TE ... -  《-》

Photodynamic therapy of hepatocellular carcinoma using tetra-triethyleneoxysulfonyl zinc phthalocyanine as photosensitizer.

The palliative treatment options for advanced hepatocellular carcinoma (HCC) are currently not satisfying. The use of photodynamic therapy (PDT) has gained much attention in the treatment of several cancers and has been approved as an alternative approach in treating different forms of cancers. We investigated for the first time the PDT effects of tetra-triethyleneoxysulfonyl zinc phthalocyanine (ZnPc) on HCC cells. Photoactivation of ZnPc loaded HCC cells resulted in a dose- and time- dependent growth inhibitory effect, the production of reactive oxygen species (ROS), induced cytotoxic effects and the induction of apoptosis in the investigated HCC cells (HepG2 and Huh-7). ZnPc-PDT inhibited the proliferation of HCC cells by up to 90% accompanied by a down-regulation of the activity and expression of the proliferation relevant mitogen-activated protein kinase (MAPK)-protein extracellular signal-regulated (ERK ½). Moreover, an up-regulation of proapoptotic BAX and a down-regulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) expressions were observed with both proteins implicated in mitochondria-driven apoptosis. The investigation of the anti-tumor effect of ZnPc-PDT in vivo using the chicken chorioallantoic membrane assays (CAM) revealed a strong reduction in the size of HCC tumor plagues >80% after 4 days of PDT-treatment without affecting the survival of the developing embryo. The pronounced anti-proliferative and anti-tumor effects of ZnPc-PDT both in vitro and in vivo render ZnPc-PDT as a promising palliative treatment option for hepatocellular carcinoma.

Ogbodu RO ，Nitzsche B ，Ma A ，Atilla D ，Gürek AG ，Höpfner M ... -  《-》

Intracellular distribution and mechanisms of actions of photosensitizer Zinc(II)-phthalocyanine solubilized in Cremophor EL against human hepatocellular carcinoma HepG2 cells.

Zinc(II)-phthalocyanine (ZnPc) is a metal photosensitizer. In the present study, we formulated the poorly-soluble ZnPc in Cremophor EL solution to enhance its solubility and determined its intracellular distribution and mechanisms of action on human hepatocellular carcinoma HepG2 cells. ZnPc uptake by the cells reached a plateau by 8h. ZnPc primarily located in mitochondria, lysosome and endoplasmic reticulum. The concentration-growth inhibition curves of ZnPc on the cell lines were pharmacodynamically enhanced by 10-50 folds by irradiation. Once irradiated, ZnPc produced significant amount of reactive oxygen species (ROS), activated caspase-3 and caspase-9, arrested cell cycle mainly at G2/M stage, and decreased membrane potential (ΔΨm) of HepG2 cells. In conclusion, the present study first elucidated cellular and molecular mechanisms of ZnPc on HepG2 cells.

Shao J ，Dai Y ，Zhao W ，Xie J ，Xue J ，Ye J ，Jia L ... -  《-》

Ultradeformable liposome loaded with zinc phthalocyanine and [Ru(NH.NHq)(tpy)NO](3+) for photodynamic therapy by topical application.

Ultradeformable liposomes (UDLs) as a drug delivery system (DDS), prepared from the unsaturated phospholipid, dioleylphosphocholine (DOPC), and containing the non-ionic surfactant Tween 20 as edge activator, have been explored as topical vehicles for zinc phthalocyanine (ZnPc) and the nitrosyl ruthenium complex [Ru(NH.NHq)(tpy)NO]3+ (RuNO) as a photosensitizers for co-generation of 1O2 and NO as reactive species, respectively. However, in order to ensure that ZnPc was present in the UDLs in its monomeric form - essential for maximal ZnPc photophysical properties - it was necessary to replace 40wt% of the DOPC with the saturated phospholipid, dimyristoylphosphocholine (DMPC). The resultant ZnPc and complex [Ru(NH.NHq)(tpy)NO]3+ containing UDLs were stable for at least a month when stored at 4°C, six times more elastic/deformable than conventional liposome (c-Ls), i.e. liposome prepared using the same weight ratio of lipids but in the absence of Tween 20, and to significantly enhance the in vitro permeation of ZnPc across fresh pig ear skin. The UDLs DDS incorporating ZnPc and [Ru(NH.NHq)(tpy)NO]3+ were toxic (by the MTT assay) towards B16-F10 melanoma cells when irradiated with visible light at 670nm, the maximum absorption of ZnPc, and at a dose of 3.18J/cm2, but not when applied in the absence of light as expected. Based on these results it is proposed that the novel topical UDLs formulation developed is a suitable delivery vehicle for photodynamic therapy.

de Lima RG ，Tedesco AC ，da Silva RS ，Lawrence MJ ... -  《-》

In vitro evaluation of combined hyperthermia and photodynamic effects using magnetoliposomes loaded with cucurbituril zinc phthalocyanine complex on melanoma.

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTT method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p>0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma.

Bolfarini GC ，Siqueira-Moura MP ，Demets GJ ，Morais PC ，Tedesco AC ... -  《-》