aluminum-tetrasulfophthalocyanine and Neoplasms

The pros and cons of purging of either bone marrow or peripheral blood stem cell preparations for autologous transplantation for cancer has been debated strongly over the past decade. Recent data implicating the role of minimal residual disease in autografted marrow in cancer relapse have renewed interest in this question. There is a considerable body of literature supporting the possibility that photosensitizer molecules in combination with light might provide a therapeutic window permitting selective elimination of malignant stem cells while sparing those of normal lineage. Molecules of this class are known to be taken up more actively by most malignant cells, and intracellular concentrations are critical in their cytotoxic effect when they are activated by light at an appropriate wavelength. The present paper reviews the observations made over the past decade on a variety of photosensitizers and their effects on hemopoietic progenitors.

Topics: Bone Marrow Purging; Bone Marrow Transplantation; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hematoporphyrin Derivative; Humans; Indoles; Light; Neoplasms; Neoplastic Stem Cells; Organometallic Compounds; Photosensitizing Agents; Porphyrins; Pyrimidinones

Topics: Antineoplastic Agents; Follow-Up Studies; Hematoporphyrin Derivative; Humans; Indoles; Lasers; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Spectrometry, Fluorescence; Time Factors

Topics: Animals; Carboxylic Acids; Combined Modality Therapy; Female; HeLa Cells; Humans; Hyperthermia, Induced; Indoles; Mice; Mice, Inbred BALB C; Mice, Nude; Nanostructures; Neoplasms; Optical Imaging; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Polymers; Pyrroles; RAW 264.7 Cells; Theranostic Nanomedicine; Thermography

To monitor a real-time follow-up of tumor response to photodynamic therapy (PDT) by dynamic 2-deoxy-2-[(18)F]fluoro-d-glucose ((18)FDG) and positron emission tomography (PET) using two photosensitizing drugs in vivo, and to assess their mechanisms of action.. Two types of photosensitizers with different action mechanisms were used in rats implanted with two tumors: AlPcS4 mainly affecting the tumor vascular system, and ZnPcS2 largely inducing direct cell kill. Twenty-four hours after administration of either photosensitizer, one tumor served as control while the other was treated with red light during 30min within the 2h PET imaging by infusion of (18)FDG. The usual two-tissue compartment kinetic model was modified to take into account the perturbation of the treatment during imaging.. The illumination of the tumors during PET imaging provoked a net decrease of (18)FDG uptake in tumors treated with AlPcS4 and a near total absence of (18)FDG uptake in tumors treated with ZnPcS2. After the end of illumination, the tumors regained (18)FDG uptake with a more pronounced uptake in the tumors treated with ZnPcS2. The rate constant values of the new (18)FDG kinetic model reflected the response of the tumors to the treatment in both photosensitizers.. Dynamic PET imaging can be used to quantitatively assess in vivo and in real-time the response of tumors to treatments. It is demonstrated that the 30min of treatment was not sufficient to reduce the activity of the tumors. The technique could be extended to directly monitor the effects of drugs in vivo.

Topics: Animals; Disease Models, Animal; Glucose-6-Phosphate; Indoles; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Positron-Emission Tomography; Rats

A layer-by-layer (LbL) assembly strategy was used to incorporate high concentrations of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) photosensitizer (PS) onto plasmonic Au nanorings (Au NRs) for increasing the cellular uptake of AlPcS4 and subsequently enhancing the efficacy of photodynamic therapy (PDT) of human breast cancer cells (MDA-MB-231) in the near-infrared (NIR) range. Au NRs with two layers of AlPcS4 (Au NR/(AlPcS4)2) markedly increased the cellular internalization of AlPcS4 and elevated the generation of reactive oxygen species (ROS). Quenching the photosensitivity of AlPcS4 on the Au NR surface during the uptake and then significant ROS formation only upon PS release inside the cellular compartment made it possible to achieve a high PDT specificity and efficacy. PDT of breast cancer cells following 4 h of incubation with various formula revealed the following cell destruction rate: ∼10% with free AlPcS4, ∼23% with singly layered Au NR/(AlPcS4)1 complex, and ∼50% with doubly layered Au NR/(AlPcS4)2. Incubation with Au NR/(AlPcS4)2 for an additional 2 h resulted in ∼85% cell killing, more than 8-fold increase compared to AlPcS4 alone. Together, integration of LbL of PS with Au NRs holds a significant promise for PDT therapeutic treatment of a variety of cancers.

Topics: Cell Line, Tumor; Gold; Humans; Indoles; Metal Nanoparticles; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species

The aim of our study was to determine if electroporation could improve the efficacy of photodynamic tumor therapy. A disadvantage of photodynamic therapy is a slow and in some cases insufficient accumulation of photosensitizer in tumor tissue, which could restrict the achievement of an efficient dose. Under the action of electric pulses, cells undergo membrane electroporation, which results in an increased permeability to various exogenous molecules. In this study, murine hepatoma MH22A cells were exposed to light in vitro in the presence of a photosensitizer, either chlorin e6 or aluminum phthalocyanine tetrasulfonate, following electroporation. Accumulation of the photosensitizers was registered by fluorescence microscopy. Cell viability was determined by the MTT assay. Our results demonstrate that electroporation improves an access of chlorin e6 and aluminum phthalocyanine tetrasulfonate to MH22A cells. Electroporation in combination with photosensitization significantly reduces viability of the treated cells even at low doses of photosensitizers.

Topics: Animals; Cell Line, Tumor; Chlorophyllides; Electrochemotherapy; Electroporation; Humans; Indoles; Microscopy, Fluorescence; Neoplasms; Organometallic Compounds; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents

A brief summary of the mechanisms involved in photodynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocyanines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus penton base proteins contain the arginine-glycine-aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteins via one or two caproic acid spacer chains (A1 or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L-tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption and in vitro photocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT-6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2-protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1 preparations. The penton base-AlPcS4A2 derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT-6 tumor implants demonstrated that the free AlPcS4A2 induced complete tumor regression at a dose of 1 mumol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adj. A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2 required 0.5 mumol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT.

Topics: Animals; Capsid; Humans; Indoles; Mastadenovirus; Mice; Mice, Inbred BALB C; Neoplasms; Neoplasms, Experimental; Organometallic Compounds; Pharmaceutical Vehicles; Photochemistry; Photochemotherapy; Photosensitizing Agents; Tryptophan; Tumor Cells, Cultured