Aluminum Phthalocyanine Tetrasulfonate Research Articles

Modulation of heat shock protein expression and cytokine levels in MCF-7 cells through photodynamic therapy.

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.

Lysosome-targeted photodynamic treatment induces primary keratinocyte differentiation

Photodynamic therapy is an attractive technique for various skin tumors and non-cancerous skin lesions. However, while the aim of photodynamic therapy is to target and damage only the malignant cells, it unavoidably affects some of the healthy cells surrounding the tumor as well. However, data on the effects of PDT to normal cells are scarce, and the characterization of the pathways activated after the photodamage of normal cells may help to improve clinical photodynamic therapy.In our study, primary human epidermal keratinocytes were used to evaluate photodynamic treatment effects of photosensitizers with different subcellular localization. We compared the response of keratinocytes to lysosomal photodamage induced by phthalocyanines, aluminum phthalocyanine disulfonate (AlPcS2a) or aluminum phthalocyanine tetrasulfonate (AlPcS4), and cellular membrane photodamage by m-tetra(3-hydroxyphenyl)-chlorin (mTHPC). Our data showed that mTHPC-PDT promoted autophagic flux, whereas lysosomal photodamage induced by aluminum phthalocyanines evoked differentiation and apoptosis. Photodamage by AlPcS2a, which is targeted to lysosomal membranes, induced keratinocyte differentiation and apoptosis more efficiently than AlPcS4, which is targeted to lysosomal lumen. Computational analysis of the interplay between these molecular pathways revealed that keratin 10 is the coordinating molecular hub of primary keratinocyte differentiation, apoptosis and autophagy.

In vitro inhibitory effect of aluminum phthalocyanine tetrasulfonate chloride against Leishmania (Viannia) Peruviana and Leishmania (Viannia) Braziliensis.

To evaluate the in vitro photodynamic activity of aluminum phthalocyanine tetrasulfonate chloride (AlPcClS4) on promastigotes and amastigotes of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. The activity of photodynamic therapy using AlPcClS4 on Leishmania promastigote and amastigotes was determined by the Methyl Thiazole Tetrazolium (MTT) colorimetric method and quantitative PCR, respectively. Photodynamic treatment showed an inhibitory effect on promastigotes, particularly on Leishmania (V.) peruviana, to a lesser extent on Leishmania (V.) braziliensis and also on intracellular forms of both species. At 24 hours post-radiation, using concentrations of 200 μM and 350 μM, the inhibitory effect on Leishmania (V.) peruviana was 72.9% and 73.9% respectively; at 96 hours the inhibitory effect was of 78.8% and 80.6%, respectively. Regarding intracellular forms, the inhibitory effect on Leishmania (V.) peruviana amastigotes was 57.8% at 72 hours post-treatment, using a concentration of 200 μM. The IC50 was 56.5, 50, 44 and 39.7 μM, at 24, 48, 72 and 96 hours post-radiation, respectively. Photodynamic therapy using AlPcClS4 against Leishmania species showed encouraging results, mainly on Leishmania (V.) peruviana, suggesting a potential use as an alternative or complement to the usual treatment of tegumentary leishmaniasis. However, new trials are still required to determine the selectivity index for the intracellular form of the parasite, and to develop methods to facilitate the efficient entry of the molecule into the host cell and the parasite.

Mesenchymal stromal cells mediated delivery of photoactive nanoparticles inhibits osteosarcoma growth in vitro and in a murine in vivo ectopic model

BackgroundOsteosarcoma (OS) is an aggressive malignant neoplasm that still suffers from poor prognosis in the case of distal metastases or occurrence of multi-drug resistance. It is therefore crucial to find novel therapeutic options able to go beyond these limitations and improve patients’ survival. The objective of this study is to exploit the intrinsic properties of mesenchymal stromal cells (MSCs) to migrate and infiltrate the tumor stroma to specifically deliver therapeutic agents directly to cancer cells. In particular, we aimed to test the efficacy of the photoactivation of MSCs loaded with nanoparticles in vitro and in a murine in vivo ectopic osteosarcoma model.MethodsAlPcS4@FNPs were produced by adding tetra-sulfonated aluminum phthalocyanine (AlPcS4) to an aqueous solution of positively charged poly-methyl methacrylate core-shell fluorescent nanoparticles (FNPs). The photodynamic therapy (PDT) effect is achieved by activation of the photosensitizer AlPcS4 in the near-infrared light with an LED source. Human MSCs were isolated from the bone marrow of five donors to account for inter-patients variability and used in this study after being evaluated for their clonogenicity, multipotency and immunophenotypic profile. MSC lines were then tested for the ability to internalize and retain the nanoparticles, along with their migratory properties in vitro. Photoactivation effect was evaluated both in a monolayer (2D) co-culture of AlPcS4@FNPs loaded MSCs with human OS cells (SaOS-2) and in tridimensional (3D) multicellular spheroids (AlPcS4@FNPs loaded MSCs with human OS cells, MG-63). Cell death was assessed by AnnexinV/PI and Live&Dead CalceinAM/EthD staining in 2D, while in the 3D co-culture, the cell killing effect was measured through ATP content, CalceinAM/EthD staining and TEM imaging. We also evaluated the effectiveness of AlPcS4@FNPs loaded MSCs as delivery systems and the ability of the photodynamic treatment to kill cancer cells in a subcutaneous mouse model of OS by bioluminescence imaging (BLI) and histology.ResultsMSCs internalized AlPcS4@FNPs without losing or altering their motility and viability in vitro. Photoactivation of AlPcS4@FNPs loaded MSCs induced high level of OS cells death in the 2D co-culture. Similarly, in the 3D co-culture (MSCs:OS ratios 1:1 or 1:3), a substantial decrease of both MSCs and OS cells viability was observed. Notably, when increasing the MSCs:OS ratio to 1:7, photoactivation still caused more than 40% cells death. When tested in an in vivo ectopic OS model, AlPcS4@FNPs loaded MSCs were able to decrease OS growth by 68% after two cycles of photoactivation.ConclusionsOur findings demonstrate that MSCs can deliver functional photosensitizer-decorated nanoparticles in vitro and in vivo and inhibit OS tumor growth. MSCs may be an effective platform for the targeted delivery of therapeutic nanodrugs in a clinical scenario, alone or in combination with other osteosarcoma treatment modalities.

Imaging of singlet oxygen feedback delayed fluorescence and lysosome permeabilization in tumor in vivo during photodynamic therapy with aluminum phthalocyanine.

.Significance: Singlet oxygen is a key cytotoxic agent in photodynamic therapy (PDT). As such, its imaging is highly desirable, but existing direct imaging methods are still limited by the exceptionally low yield of the luminescence signal. Singlet oxygen feedback delayed fluorescence (SOFDF) of the photosensitizer is a higher yield alternative for indirect measurement of this signal.Aim: The aim was to explore feasibility of SOFDF imaging in vivo in tumor-bearing mice during PDT and investigate how SOFDF images can be transformed into images of singlet oxygen. In addition, we study whether lysosome permeabilization can be visualized through fluorescence lifetime.Approach: Mice were intravenously injected with 2.5 mg/kg of photosensitizer aluminum(III) phthalocyanine tetrasulfonate () 20 h prior to experiments, having subcutaneous BxPC3 pancreas tumors. Time-resolved delayed fluorescence and prompt fluorescence (PF) were imaged using an intensified time-gated camera with 10-Hz pulsed laser excitation at 690 nm.Results: Delayed emission from was detected with lifetimes 7 to , which was attributed to SOFDF and shown to be oxygen-dependent. Singlet oxygen images were approximated by the ratio of SOFDF/PF at each pixel. SOFDF images of a good quality could be captured within several seconds with a radiant exposure of . In addition, lifetime images of PF in ns-time domain enabled us to visualize the event of lysosome permeabilization, as the lifetime increased from to 5.2 ns.Conclusions: Imaging of SOFDF in vivo in mouse tumor during PDT with is feasible, and it is a promising method for singlet molecular oxygen monitoring. Moreover, the time-gated approach also enables visualization of the lysosome permeabilization that alters the PF lifetime.

Genotoxic effects of photodynamic therapy in laryngeal cancer cells - An in vitro study.

Recently, the use of photodynamic therapy grows as an alternative treatment for cancer, since it has a noninvasive characteristic and affinity to the tumor tissue. Accordingly, understanding the therapy's foci of action is important for the technique improvement. This work aims to understand the genotoxic effect triggered by the therapy action, thus evidencing the permanent changes caused to the genetic material of the tumor cell after the treatment. Therefore, to increase the knowledge in this study field, the methodology of the comet assay and count of micronucleus formed after the therapy was adopted in order to understand if the damage caused to the DNA of tumor cell makes its replication process unfeasible in future generations. The study allows a better therapeutic approach to the cancer treatment, making the process of association between therapies a more effective option during the disease treatment.

Intercalation of Bioactive Molecules into Nanosized ZnAl Hydrotalcites for Combined Chemo and Photo Cancer Treatment

Hydrotalcites-like compounds, also known as anionic clays or layered double hydroxides, represent the only example of lamellar solid with positively charged layers and exchangeable interlayer anions. In this study, a nanostructured HTlc with formula [Zn0.72Al0.28(OH)2] Br0.28·0.69 H2O was used as inorganic drug delivery system for anticancer therapy. Two different molecules were selected for being separately intercalated into ZnAl-HTlc: the anticancer drug norcantharidin, known for inducing cell cycle arrest at G2/M phase, and the tetra-sulfonated aluminum phthalocyanine, a photosensitizer used in anticancer photodynamic therapy. The obtained hybrid ZnAl-HTlc, were characterized in terms of X-ray powder diffraction pattern, thermogravimetric analysis, scanning electron microscopy, drug release profile, in vitro cytotoxicity, and ability to produce ROS and 1O2 upon light irradiation. Our results clearly indicate that the two selected compounds are efficiently intercalated within HTlc layers. Moreover, in v...

Functionalized poly(pyrrole-3-carboxylic acid) nanoneedles for dual-imaging guided PDT/PTT combination therapy

Herein, poly(pyrrole-3-carboxylic acid) (PPyCOOH) nanoneedles with abundant carboxyl groups were synthesized by aqueous dispersion polymerization method using pyrrole-3-carboxylic acid as conductive polymer monomer. The PPyCOOH nanoneedles not only owned good photothermal performance, but also more importantly showed enhanced tumor cell uptake efficiency (1.64 fold) compared with size and zeta-potential matched nanospheres. After loading photosensitizer aluminum phthalocyanine tetrasulfonate (AlPCS4) and modifying with poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) onto the PPyCOOH nanoneedles, novel nanoneedle complexes (AlPCS4@PPyCONH-PAH-PAA) integrating photodynamic therapy (PDT) and photothermal therapy (PTT) were successfully fabricated. The as-prepared nanoneedle complexes improved uptake efficiency of AlPCS4 both in vitro and in vivo. Moreover, the nanoneedle complexes have infrared thermal and fluorescent properties. By combined PDT/PTT under the guiding of dual modal imaging, the tumors in mice were completely eliminated and no recurrence was observed in 30 days after treatment, indicating that PPyCOOH nanoneedles have great potential as a novel drug carrier for constructing multifunctional nanoplatform used for cancer treatment.

Cyanine dyes as ratiometric fluorescence standards for the far-red spectral region.

Most quantitative fluorescence measurements report emission quantum yields by referring the integrated fluorescence profile to that of a well-known standard compound measured under carefully controlled conditions. This simple protocol works well provided an appropriate standard fluorophore is available and that the experimental conditions used for reference and unknown are closely comparable. Commercial fluorescence spectrophotometers tend to perform very well at wavelengths between 250 and 650 nm but are less responsive at longer wavelengths. There are no recognized emission standards for the far-red region. We now report fluorescence quantum yields for a series of commercially available cyanine dyes in methanol solution at room temperature. The compounds are selected to span the wavelength region from 600 to 850 nm, with absolute emission quantum yields being determined by thermal blooming spectrometry. Calibration of the instrument is made by reference to aluminium(iii) phthalocyanine tetrasulfonate and aza-BODIPY in methanol.

Efficacy of Methylene Blue and Aliminium Phthalocyanine Mediated Sonophotodynamic Therapy on Prostate Cancer Cell Lines

Sono-photodynamic therapy (SPDT) is a new modality for cancer treatment that uses synergetic effect of ultrasound and light to activate sensitizers and produce mechanical, sonochemical and photochemical activities to kill cancer cells. This study aims to investigate the antitumor effects and possible mechanisms of methylene blue (MB) and aluminium phthalocyanine tetrasulfonate (AlPc) mediated photodynamic therapy (PDT), sonodynamic therapy (SDT) and SPDT on prostate cancer cell lines (PC3, LNCaP) in vitro.Cell viability was measured by the use of MTT assay, apoptotic morphological characteristics were analyzed using HOPI staining and reactive oxygen species (ROS) were measured using Muse oxidative stress kit. Western blotting was employed to analyze the activity of the apoptosis related protein (Caspase proteins, PARP, Bax and Bcl-2), and the autophagy associated protein (LC3, LAMP-2 and Beclin-1) expressions.The MTT results revealed that although PDT and SDT also led to a decrease in cell viability, SPDT provided a more prominent cell viability loss when compared with control, PDT and SDT groups. In all groups, MB was observed to be more cytotoxic and led to a more prominent decrease in cell viability in comparison to AlPc. There was a significant increase in the early and late apoptotic cell populations in SDT, PDT and SPDT groups. In addition, alterations in the activity of apoptosis related proteins were observed in SPDT group. Moreover, ROS production in cells was found to be markedly increased in PDT and SPDT groups when compared to control and SDT groups.The results demonstrated that PDT or SDPT exert their action on cell viability probably via the formation of ROS species which in turn induces apoptosis and cell death. Both therapies are promising potential therapeutic strategies for the treatment of prostate cancer.

Study of the AlS4Pc-Polylysine Ion Pair, a Red-Fluorescent Probe: Its High Specificity, Large Concentration Range Response to Bismuth Ion, and Application.

Tetrasulfonated aluminum phthalocyanine (AlS4Pc), a strongly red-emitting compound, shows high detection sensitivity, little effect of photobleaching, and photochemical stability, making it an excellent red-fluorescent probe. We have observed that in acid media, a low concentration of poly-L-lysine (PLL) has a strong fluorescence-quenching effect on AlS4Pc, forming the ion-pair complex as AlS4Pc-PLL with almost no fluorescence. However, in the presence of Bi3+, the fluorescence of AlS4Pc-PLL dramatically recovers and the emission is visual because of the remarkable recovery. Screening experiments with other metal ions reveal that only Bi3+ can restore the fluorescence of the AlS4Pc-PLL complex. The presence of other metal ions does not result in the recovery of fluorescence, indicating the high specificity of the response to Bi3+ of AlS4Pc-PLL. This is the key finding of the present study. It was also observed that the response to Bi3+ of AlS4Pc-PLL exhibits a linear relationship over a large concentration range (three orders of magnitude). Based on these findings, we have established a new quantitative analysis method for Bi3+ with high specificity and high sensitivity, using the ion-pair AlS4Pc-PLL complex as a red-fluorescent probe, and we discuss the reaction mechanism. The detection limit of this method is 0.0021 mg L-1 The linear relationship applies to the range of 0.007-34.9 mg L-1 with a correlation coefficient of 0.9993. The method established addresses the complex operation and time-consuming problems in traditional methods and is thus suitable for real applications. Satisfactory results have been obtained when the method was applied to the measurement of real samples. This study further expands the scope of new applications of phthalocyanine-based red-fluorescent probes in analytical sciences.

N-acetyl Glucosamine Distribution and Mitochondrial Activity of Tumor Cell Exposed to Photodynamic Therapy.

The use of lectins can play an important role for tracking modification on cell surface components, since lectins can be easily complexed with radioisotopes, biotin or fluorescein, facilitating the evaluation of carbohydrates distribution in the cell and mitochondrial activity. The aim of this study was to evaluate photodynamic therapy effects on indirect distribution of N-acetyl-glucosamine terminal glycoproteins, in human laryngeal carcinoma HEp-2 cell line surface, using lectin wheat germ agglutinin (WGA) and on mitochondrial activity, for the same cell line, using MitoTracker. The photosensitizer Aluminum Phthalocyanine Tetrasulfonate (AlPcS4) was administrated at 10μM/mL, followed by an incubation period for its accumulation in the tumor cells, which were irradiated with laser diode λ=685nm and energy density of 4.5J/cm2. Our results indicated that, after Photodynamic Therapy (PDT), it was observed N-acetyl glucosamine terminal glycoprotein expression and mitochondrial O2 production, compared to the control group. Based on these results, we suggest that PDT influences the O2 mitochondrial production and the presence of surface glycoproteins N-acetyl glucosamine terminals.

Photosensitized production of nitric oxide and peroxynitrite from a carbon-bound diazenium diolate and 2-methyl-2-nitrosopropane

Abstract The photosensitized generation of nitric oxide from alanosine (3-(hydroxynitrosoamino)- d , l -alanine) by aluminum phthalocyanine tetrasulfonate (AlPcS4) is reported. While nitric oxide (NO) is obtained in nitrogen-saturated solutions, evidence suggest that both NO and peroxynitrite are produced in air-saturated solutions. Enhancement of NO production occurs in the presence of ubiquinone-0. These observations support the idea that NO is produced by the photosensitized oxidation of alanosine. Both NO and peroxynitrite are detected during photoirradiation of AlPcS4 in the presence of 2-methyl-2-nitrosopropane (MNP) and hypoxanthine (HX), but not in the absence of HX, in air-saturated solutions, thus implying that HX is acting as sacrificial electron donor, thus promoting superoxide formation.

Voltage-sensitive styryl dyes as singlet oxygen targets on the surface of bilayer lipid membrane

Photosensitizers are widely used as photodynamic therapeutic agents killing cancer cells by photooxidation of their components. Development of new effective photosensitive molecules requires profound knowledge of possible targets for reactive oxygen species, especially for its singlet form. Here we studied photooxidation of voltage-sensitive styryl dyes (di-4-ANEPPS, di-8-ANEPPS, RH-421 and RH-237) by singlet oxygen on the surface of bilayer lipid membranes commonly used as cell membrane models. Oxidation was induced by irradiation of a photosensitizer (aluminum phthalocyanine tetrasulfonate) and monitored by the change of dipole potential on the surface of the membrane. We studied the drop of the dipole potential both in the case when the dye molecules were adsorbed on the same side of the lipid bilayer as the photosensitizer (cis-configuration) and in the case when they were adsorbed on the opposite side (trans-configuration). Based on a simple model, we determined the rate of oxidation of the dyes from the kinetics of change of the potential during and after irradiation. This rate is proportional to steady-state concentration of singlet oxygen in the membrane under irradiation. Comparison of the oxidation rates of various dyes reveals that compounds of ANEPPS series are more sensitive to singlet oxygen than RH type dyes, indicating that naphthalene group is primarily responsible for their oxidation.

Development of near-infrared photoactivable phthalocyanine-loaded nanoparticles to kill tumor cells: An improved tool for photodynamic therapy of solid cancers

Conventional photodynamic therapy has shown to be beneficial in the treatment of a variety of tumors. However, one of its major limitations is the inadequate penetration depth of visible light. In order to overcome this constraint, we developed 80nm poly-methylmethacrylate core-shell fluorescent nanoparticles (FNP) loaded with the photosensitizer tetrasulfonated aluminum phthalocyanine (Ptl). To demonstrate the efficacy of our Ptl@FNP we performed in vitro and in vivo studies using a human prostate tumor model. Our data reveal that Ptl@FNP are internalized by tumor cells, favour Ptl intracellular accumulation, and efficiently trigger cell death through the generation of ROS upon irradiation with 680nm light. When directly injected into tumors intramuscularly induced in SCID mice, Ptl@FNP upon irradiation significantly reduce tumor growth with higher efficiency than the bare Ptl. Collectively, these results demonstrate that the newly developed nanoparticles may be utilized as a delivery system for antitumor phototherapy in solid cancers.

Structure-matched Phthalocyanine Ion Pair as a Red-emitting Fluorescent Optical Probe for the Analysis of Sodium Dodecylbenzenesulfonate with High Specificity and Sensitivity

We have found that a positively charged cationic copper phthalocyanine, Alcian blue (Alcian blue 8GX), can efficiently quench the fluorescence of an oppositely charged red fluorescent phthalocyanine compound with a matched molecular structure, tetrasulfonated aluminum phthalocyanine (AlS4Pc), because of the formation of an ion pair complex (AlS4Pc-Alcian blue 8GX) that exhibits almost no fluorescence. An investigation was carried out on the fluorescence recovery of AlS4Pc-Alcian blue 8GX caused by a series of anionic surfactants containing a sulfonic group (sodium dodecylbenzenesulfonate (SDBS), sodium lauryl sulfate (SLS), and sodium dodecyl sulfate (SDS)). The results showed that SDBS exhibited a significant response, and the highest sensitivity among the surfactants. Due to its high efficiency of fluorescence quenching and the high level of fluorescence recovery, direct observes can even be performed by the naked eye. The results revealed that the Alcian blue 8GX-AlS4Pc ion-pair complex fluorescent probe only responded to SDBS in the low-concentration range. Based on the new founding, this study proposed a novel principle and method of fluorescence enhancement to specifically measure the concentration of SDBS, thereby achieving a highly sensitive and highly specific determination of SDBS. Under the optimal conditions, the fluorescence intensity (I(f)) of the system and the concentration of SDBS in the range of 1 × 10(-7) - 1 × 10(-5) mol/dm(3) exhibited a good linear relationship. This method is highly sensitive, and the operation is simple and rapid. It had been applied for the quantitative analysis of SDBS in environmental water, while achieving satisfactory results compared with those of the standard method. This study developed a new application of the fluorescent phthalocyanine compounds used as molecular probes in analytical sciences.

Evaluation of photodynamic therapy in adhesion protein expression.

Photodynamic therapy (PDT) is a treatment modality that has clinical applications in both non-neoplastic and neoplastic diseases. PDT involves a light-sensitive compound (photosensitizer), light and molecular oxygen. This procedure may lead to several different cellular responses, including cell death. Alterations in the attachment of cancer cells to the substratum and to each other are important consequences of photodynamic treatment. PDT may lead to changes in the expression of cellular adhesion structure and cytoskeleton integrity, which are key factors in decreasing tumor metastatic potential. HEp-2 cells were photosensitized with aluminum phthalocyanine tetrasulfonate and zinc phthalocyanine, and the proteins β1-integrin and focal adhesion kinase (FAK) were assayed using fluorescence microscopy. The verification of expression changes in the genes for FAK and β1 integrin were performed by reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that HEp-2 cells do not express β-integrin or FAK 12 h following PDT. It was concluded that the PDT reduces the adhesive ability of HEp-2 cells, inhibiting their metastatic potential. The present study aimed to analyze the changes in the expression and organization of cellular adhesion elements and the subsequent metastatic potential of HEp-2 cells following PDT treatment.

Effect of photodynamic therapy supplemented with quercetin in HEp‐2 cells

Photodynamic therapy (PDT) is a technique that can be used as a complementary therapy in cancer treatment combined with other therapeutic modalities. Quercetin (QCT) is known to be effective in the treatment of cancer, by reducing the cell viability of different cancer cell lines. This study aimed to evaluate the influence of different concentrations of QCT in PDT on the viability, mitochondrial membrane potential and induction of apoptosis/necrosis in the human larynx carcinoma cells (HEp-2). The HEp-2 cells were treated with aluminum phthalocyanine tetrasulfonate (AlPcS4) and QCT and subsequently irradiated with a diode laser light (685 nm, 35 mW, 4.5 J/cm(2)). The results demonstrated that treatment of HEp-2 cells with high concentrations of QCT (at least 50 μM) reduced cell viability. This response was enhanced in cells subjected to PDT supplemented with high concentrations of QCT. In addition, was observed decrease in the mitochondrial membrane potential and characteristics of late apoptosis and/or initial necrosis process. QCT at concentrations from 50 μM improves PDT-induced cytotoxicity by significantly reducing cell viability by apoptosis and/or necrosis, and mitochondrial membrane potential of Hep-2 cells.

Poly(amidoamine) dendrimer-grafted porous hollow silica nanoparticles for enhanced intracellular photodynamic therapy

We report a novel photodynamic therapy (PDT) drug-carrier system, whereby third-generation (G3) polyamidoamine (PAMAM) was successfully grafted to the surface of porous hollow silica nanoparticles (PHSNPs), followed by the attachment of gluconic acid (GA) for surface charge tuning. The composite G3-PAMAM-grafted PHSNPs (denoted as G3-PHSNPs) with a diameter range of 100–200nm and about 30nm sized shell thickness retain bimodal pore structures (e.g. inner voids and porous structure of the shells) and PAMAM-functionalized outer layer with a large number of amino groups, allowing high loading efficacy of aluminum phthalocyanine tetrasulfonate (AlPcS4) and its effective release to target tissue. The GA-induced G3-PHSNPs were evidenced to be able to favorably cross tumor cell walls and enter into the cell interior. The generation of singlet oxygen (1O2) from AlPcS4-GA-G3-PHSNPs under visible light excitation was detected by the in situ electron spin resonance measurements and the oxidative reaction between the generated 1O2 and a chemical probe. In vitro cellular experiments showed that the photosensitive GA-G3-PHSNPs exhibited a good biocompatibility in the dark and a higher killing efficacy against MCF-7 tumor cells upon irradiation as compared with free AlPcS4, which implies that the preformed photosensitive drug-carrier system might be potentially applicable in PDT.

Topical photodynamic therapy using transfersomal aluminum phthalocyanine tetrasulfonate: in vitro and in vivo study

The efficacy of transfersomes (flexible liposomes) as a novel technique for topical delivery of the hydrophilic tetra-anionic photodynamic sensitizer aluminum (III) phthalocyanine tetrasulfonate (AlPcS4) was investigated, on mammalian fibroblasts and on Balb/c mice dorsal skin. AlPcS4 was loaded in transfersomes composed of phosphatidylcholine/sodium deoxycholate (5:1, 10:1, and 15:1 w/w, ratios), resulting in 110-, 160-, and 200-nm mean size vesicles with encapsulation efficiencies of 16, 25, and 30%, respectively. In vitro studies on baby hamster kidney-21 fibroblasts revealed twofold enhancement of the photocytotoxicity of AlPcS4 loaded in transfersomes (Trans-AlPcS4), compared to free AlPcS4 dissolved in culture medium. The photocytotoxicity of Trans-AlPcS4 was less dependent on the incubation time with cells, compared to free AlPcS4. Topical application on the dorsal skin of Balb/c mice revealed that both free AlPcS4 and Trans-AlPcS4 exhibited evident photosensitization towards mice skin, but acquiring different regions of skin.