Metal remover

Various adsorbents are available for the removal of heavy and toxic metals, silica-based materials have been the most popular. Recently, there has been considerable interest for the modification of organic moieties and mesostructured materials to enable their use as efficient adsorbent for metal removal. In this study, here we are reporting successful incorporation of tetrakis(4-carboxyphenyl)porphyrin (TCPP) in mesoporous silica by the post-synthetic method. TCPP-SBA-15 has been found to be an effective material for the removal of Cu(II) from aqueous solution due to the chelating nature of the porphyrin-bridging group. A comparative study on adsorption of copper(II) ion over NH2-SBA-15 silica and TCPP-SBA-15 was performed. The results show that TCPP-SBA-15 material has higher adsorption capacity than NH2-SBA-15 silica and it reaches the adsorption maxima around 13 mmol g−1. [1]

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The powder low angle X-ray diffraction patterns of NH2-SBA-15 and TCPP-SBA-15 are shown in Fig. 1a. All the samples showed three well-resolved diffraction peaks, with a very intense peak at 2θ of 0.9–1.18° and two peaks with at 2θ of 1.4–1.8°. These peaks could be indexed to the (1 0 0), (1 1 0), and (2 0 0) planes, which correspond to a mesostructure of hexagonal space group symmetry p6mm. The XRD pattern of TCPP-SBA-15 show strong (1 0 0) peaks, which suggests the framework stability of the mesoporous material, is well maintained when the TCPP is functionalized on the NH2-SBA-15. The relative intensities of the (1 1 0) and (2 0 0) peaks in the TCPP-SBA-15 pattern were lower than those in the NH2-SBA-15, thereby indicating that the porphyrins are dispersed in the mesoporous channels. Nitrogen adsorption–desorption isotherms for all materials were found to be type IV curve, with well-defined capillary condensation step, characteristic of uniform mesoporous materials (Fig. 1b). The surface area is evaluated from nitrogen adsorption isotherms by using the BET equation. Pore size was calculated by the Barrett–Joyner–Halenda (BJH) method using desorption branch of the adsorption–desorption isotherms. Specific surface areas and mesopore diameters for NH2-SBA-15 and TCPP-SBA-15 are shown in Table 1. The tendencies of mesopore shrinkage with incorporation TCPP is exhibited by changes in the surface area and total pore volume, which indicate get worse mesostructural features with loading of TCPP groups. [1]

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The incorporation of TCPP into mesoporous silica was confirmed by Fourier-transform infrared (FT-IR) spectroscopy (Fig. 3). In the FT-IR spectrum of NH2-SBA-15, the peaks around 1628 cm−1 were assigned to asymmetric NH2 stretching (νasNH2) and NH2 deformation (δNH2) [27], and that broad peak at 3300 cm−1 could be attributed to the overlap between secondary amine (NH) stretching (νNH) and symmetric NH2 stretching (νsNH2). The FT-IR spectrum of TCPP-SBA-15 revealed peaks at 1713 and 1527 cm−1. These peaks were assigned to the Cdouble bondO stretching vibration of TCPP and the NH2 deformation (δNH2) of the amide group, respectively. The amide group is formed when the carboxyl acid group of TCPP reacts with the amino group on SBA-15. OH stretching of the carboxyl acid group of TCPP (3645 cm−1), overtone of Si–O–Si lattice vibration (1984 and 1850 cm−1), and CH2 stretching (2863 and 2929 cm−1) were also observed in this spectrum. [1]

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The presence of TCPP on SBA-15 was also confirmed by UV–vis spectroscopy (Fig. 4). The TCPP spectrum showed Soret band (417 nm) and four weak Q-bands. TCPP-SBA-15 showed absorption bands at 414 nm (Soret band) and at 514, 548, 591, and 647 nm. This result suggests that TCPP was functionalized onto SBA-15 (as characterized by a blue shift of the Soret band associated with a significant amount of TCPP) during the preparation process. When TCPP was functionalized onto SBA-15, the polarity in the vicinity of TCPP increases, as evidenced by the shifts of the absorption bands towards a higher energy. [1]

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After the demetallation reaction, TCPP-SBA-15 was separated and washed. After washing, UV–vis spectroscopic studies were conducted. The UV–vis spectrum of TCPP-SBA-15 containing adsorbed Cu(II) ions is similar to that of Cu-TCPP, which shows a Soret band at 417 nm and two Q-bands at 540 and 583 nm. It is thus observed that Cu molecules were chelated with central nitrogen ligands in TCPP. An adsorption experiment was performed to investigate the effect of TCPP on the mesoporous silica at different Cu(II) ion concentrations (between 65 and 1065 mg L−1). Comparative experiment was carried out the same condition for the mesoporous silica without TCPP. The adsorption rate has been analyzed using Eq. (1) and plotted in Fig. 5. The Cu(II) concentration was increased from 65 to 1065 mg L−1 in order to attain the plateau values representing the saturation of the active points which are available for interaction with metal ions on TCPP-SBA-15; in other words, the Cu(II) concentration was increased in order to obtain the maximum removal capacities for the metal ions of interest. The maximum adsorption of Cu(II) on the TCPP-SBA-15 sample was 13 mmol of Cu(II) per gram of the adsorbent (Table 2). In addition, high removal rates were observed at the beginning of the experiment, after which equilibrium values were gradually attained within 60 min. Demetallation experiments are usually completed within 1 h, which indicates that the binding process is considerably rapid. This high adsorption capacity was accomplished by the incorporation of porphyrin groups into the silica structure (Fig. 5). As noted earlier, the chelating properties of the porphyrin-bridging group affect the process of metal removal in water. The high affinity of the porphyrin group towards Cu(II) ions resulted in a very high adsorption capacity. The high sorption rates can also be attributed to the uniform porous structure of the material, as characterized by the presence of regular mesochannels. [1]

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The efficiency of the TCPP-SBA-15 was also studied towards a waste water sample collected from car paint industry, initially the effluent sample contains 32 mg L−1 of Cu2+ ion within a short time period of 15 min the concentration of the Cu2+ have been reduced to half (15 mg L−1). It is found that after 200 min no Cu2+ was observed in the effluent sample as suggested by the ICP-MS studies. Therefore it can be considered as effective system for removal of copper. The distribution coefficient (Kd) is used for evaluating the affinity of the adsorbent towards Cu(II) ions. The distribution coefficients are summarized in Table 2. In the case of TCPP-SBA-15, Kd increases, indicating that the affinity towards Cu(II) ions increases with the loading of TCPP groups. The fact that the considerable affinity of TCPP groups towards Cu(II) species gives rise to the high distribution coefficient is important from the environmental perspective. The removal capacities of Cu(II) ions at different initial concentrations, as calculated by Eq. (3), are also listed in Table 2. [1]

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(3) The recovery of Cu(II) and regeneration of the adsorbent are key processes. In order to perform these two processes and to measure the practical utility of the adsorbent, desorption experiments were carried out by treating 0.1 g of TCPP-SBA-15 containing adsorbed Cu2+ ions with 50 mL of 0.2 M HCl solution over a period of 1 h. Since 0.2 M HCl solution was used, H+ could replace the metal ions adsorbed by TCPP-SBA-15. Fig. 6 shows the desorption rate of TCPP-SBA-15–metal ion complexes as a function of time. The desorption process reached equilibrium at 60 min and the desorption rate was 65.1% for Cu(II) (Fig. 6a). [1]

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Reusability experiments were performed on TCPP-SBA-15 using the same procedure as that followed in the adsorption experiments. Adsorption–desorption cycles were repeated 3 times using the same material (Fig. 6b). The adsorption capacities were found to be around 11.906 mmol g−1 after the first cycle, 11.760 mmol g−1, after the second cycle and 11.630 mmol g−1 after the third cycle. Desorption of the Cu complex onto TCPP-SBA-15 was monitored by UV–vis spectroscopy (Fig. 7a). The UV–vis spectra of Cu-free TCPP-SBA-15 include two major features: a series of visible bands (Q-bands) and an extremely intense band (Soret band). Similar to the spectra of most free-base tetrakis(4-carboxyphenyl)porphyrin, that of Cu-free TCPP-SBA-15 shows well-defined Q bands that are assigned to the 0 → 0 and 0 → 1 vibronic transitions of the distinct x and y components of the lowest π → π* transition. This proves that Cu(II) was recovered during the desorption process. The spectrum of the reused adsorbent shows bands similar to those in the spectrum of Cu-tetrakis(4-carboxyphenyl)porphyrin, which also has a Soret band at 417 nm and Q-bands at 540 and 583 nm (Fig. 7a). To confirm the presence of Cu(II) ions inside TCPP-SBA-15, we performed EPR studies on TCPP-SBA-15 samples containing adsorbed Cu(II) ions (Fig. 7b). The EPR spectrum of the TCPP-SBA-15 samples containing adsorbed Cu(II) ions can be explained in terms of an axial spin Hamiltonian with parameters g|| = 2.20 and g⊥ = 2.06, which indicates that the Cu(II) ions linked to nitrogen ligands in TCPP have a square planar symmetry (Fig. 7b) [1].

Adsorption test [1]
Demetallation experiments was carried out by stirring 100 mg of TCPP-SBA-15 in 250 mL of a metal solution at 25 °C. Two different Cu2+ concentrations viz. 1065 and 65 mg L−1 were performed. NH2-SBA-15 was also conducted the same adsorption test. The solution from each vial was analyzed for Cu2+ concentration after different time intervals and removal rate of Cu2+ was calculated using Eq. (1).
where Qe is quantity of Cu2+ adsorbed on the TCPP-SBA-15 at the time of equilibrium (mg/g), C0 is initial concentration of Cu2+ in aqueous solution of CuSO4·5H2O (mg L−1), and Ce is final concentration of Cu2+ in aqueous solution of CuSO4·5H2O at the time of equilibrium (mg L−1), V is total volume of the solution (L); m mass of adsorbents (g). The distribution coefficient, Kd, for evaluating the affinity of the adsorbent for adsorbate in aqueous solution can be calculated using Eq. (2)

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The tetrakis(4-carboxyphenyl)porphyrin (TCPP) as an organic moiety was successfully incorporated onto in mesoporous silica by the post-synthetic method. Chelating properties of TCPP make this attractive adsorbent for Cu(II) ions removal from aqueous solutions. The adsorption of copper (II) on TCPP-SBA-15 was studied comparing with adsorption on NH2-SBA-15 silica. The result show that the adsorbed amount reaches the maximum around 13 mmol g−1 and TCPP-SBA-15 material has higher adsorbed capacity than NH2-SBA-15 silica. [1]

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The adsorption of Cu(II) ions on tetrakis(4-carboxyphenyl)porphyrin (TCPP)-functionalized NH2-SBA-15 was investigated. Metal adsorption on TCPP-SBA-15 was carried out using different initial concentrations of Cu(II). The maximum adsorption of Cu(II) on the TCPP-SBA-15 sample was 12.96 mmol of Cu(II) per gram of the adsorbent. The desorption process reached equilibrium at 60 min and the desorption rate for Cu(II) was 65.1%. Regeneration experiments carried out for TCPP-SBA-15 containing adsorbed Cu(II) ions revealed that the adsorption capacities were around 11.906, 11.760, and 11.630 mmol g−1after three successive adsorption–desorption cycles. Thus, we can conclude that TCPP ligands enable these materials to function as adsorbents for the removal of Cu(II) ions [1].

Absorption, Distribution and Excretion
Particle size should be optimized to achieve targeted and extended drug delivery to the affected tissues. We describe here the effects of the mean particle size on the pharmacokinetics and photothrombic activity of meso-tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable nanoparticles based on poly(d,l-lactic acid). Four batches of nanoparticles with different mean sizes ranging from 121 to 343 nm, were prepared using the emulsification-diffusion technique. The extravasations of each TCPP-loaded nanoparticle formulation from blood vessels were measured, as well as the extent of photochemically induced vascular occlusion. These preclinical tests were carried out in the chorioallantoic membrane (CAM) of the chicken's embryo. Fluorescence microscopy showed that both the effective leakage of TCPP from the CAM blood vessels and its photothrombic efficiency were dependent on the size of the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the blood vessels and the surrounding tissue increased at the applied conditions, when the particle size decreased. This suggests that large nanoparticles are more rapidly eliminated from the bloodstream. In addition, after injection of a drug dose of 1 mg/kg body weight and a drug-light application interval of 1 min, irradiation with a fluence of 10 J/sq cm showed that the extent of vascular damage gradually decreased when the particle size increased. The highest photothrombic efficiency was observed when using the TCPP-loaded nanoparticles batch with a mean diameter of 121 nm. Thus, in this range of applied conditions, for the treatment of for instance a disease like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments suggest that the smallest nanoparticles may be considered as the optimal formulation since they exhibited the greatest extent of vascular thrombosis as well as the lowest extravasation. /TCPP nanoparticles/
We studied the uptake of meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles by SW480 cells and carried out a systematic investigation of the cellular internalization mechanism of TCPP nanoparticles, also studied the photocytotoxicity of TCPP nanoparticles. At first, meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles were prepared by the method of mixing solvent techniques. SW480 cellular uptakes of photosensitizers (TCPP nanoparticles, TCPP-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and free TCPP) were analyzed by the method of fluorospectrophotometry. Endocytosis mechanism investigation was carried out by preincubating SW480 cells at 4 degrees C, and preincubating SW480 cells with sucrose, K+-free buffer solution and filipin. Clathrin HC expression after incubating SW480 cells with these three photosensitizers was analyzed by methods of Western blot and RT-PCR. At last, we analyzed the photo-cytotoxicity after incubating SW480 cells with photosensitizers and receiving irradiation. SW480 cells showed rapid uptake (0.0083 fmoles TCPP/cell) of TCPP nanoparticles after 1h incubation. We also demonstrated that the uptake of TCPP nanoparticles by SW480 cells was a clathrin-mediated endocytosis pathway. As a result of rapid internalization of TCPP nanoparticles by SW480 cells, this special photosensitizer showed very high photocytotoxic effect on SW480 cells in vitro. The nano-sized photosensitizer with no matrix cover: TCPP nanoparticles, can produce higher photocytotoxicity than other photosensitizers (TCPP-loaded PLGA nanoparticles and free TCPP). The in vivo tumor growth inhibition experiment indicated that TCPP nanoparticles plus PDT treatment induced the most dramatic tumor-inhibiting efficacy in all TCPP treated groups. The results of this study suggest that TCPP nanoparticles represent a potential and powerful photodynamic therapy agent. /TCPP nanoparticles/
Athymic nude mice with subcutaneously xenotransplanted urothelial carcinoma received intravenously injections of the synthetic sensitizer meso-tetra (4-carboxyphenyl) porphyrin. Fluorescence at the tumors and the skin was excited using a Kr+ laser (407 nm) and was detected at 652 nm using a fiberoptical sensor in combination with an optical multichannel analyzer at different times after application of the sensitizer. Photodynamic treatment was carried out using an Ar+ laser pumped dye laser (650 nm; 100 mW/sq cm; 100 J/sq cm). The delay of tumor growth was determined in a follow-up period of four weeks and was correlated to the in vivo fluorescence measurements.
Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential applications in targeted imaging and photodynamic therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide coupling with the epsilon amine group of lysine, followed by Fmoc deprotection. The resulting compounds did not dissolve well in aqueous solvent, but could be solubilized with the assistance of surfactants, including cholic acid. The l-amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP. Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in cells following incubation and irradiation with blue light. These experimental results do not provide evidence to suggest that lysine-mTCPP is able to specifically target cancer cells. However, they do highlight mTCPP as a convenient and accessible framework for assessing molecular targeting of photosensitizers. /lysine-conjugated mTCPP/

Toxicity Summary
IDENTIFICATION AND USE: Tetracarboxyphenylporphine (TCPP) is a dark blue to purple to black powder. TCPP is a potent photosensitizer activated by visible light. It has been used as a research chemical, chemical intermediate, and porphyrin dye. It has been tested for photodynamic therapy of cancer in animal cell models, and as a diagnostic noninvasive assay in lung cancer patients. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: The photosensitizing effects of TCPP on ColE1 supercoiled DNA were studied using agarose gel electrophoresis. Photoinduced single- and double-strand breaks were observed to form under neutral conditions.

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Interactions
The role of the neoplastic cell in both porphyrin localization and the photochemotherapeutic response was investigated with the use of a series of tumor-localizing porphyrins and the L1210 tumor system. In vivo photoirradiation of DBA/2Ha mice bearing L1210 solid tumors and previously given injections of meso-tetra-(4-sulfonatophenyl)-porphine, meso-tetra-(4-carboxyphenyl)-porphine, or hematoporphyrin derivative (Hpd) indicated that all three chemicals elicited a photodynamic response resulting in necrosis of exposed tissue. Isolation of tumor cells from mice given injections of porphyrin with the use of mild mechanical means and physiologic conditions followed by in vitro photoirradiation of the cells under conditions established to optimize rapid cytocidal effects resulted in no appreciable cell death. A similar situation was noted with the use of spleen cells from mice given injections of Hpd, the spleen cells presumably containing substantial amounts of porphyrin. Both fluorescence microscopy and chemical extraction and quantitation of the porphyrins in the cells indicated that the inability to elicit a rapid cytocidal effect upon in vitro photoirradiation resulted from either the absence of or the presence of only very small amounts of porphyrin. These results indicate that in this particular tumor system the neoplastic cell per se plays only a minor role in porphyrin localization and, as a consequence, cannot be readily killed upon photoirradiation, suggesting that rapid cytocidal effects, due solely to porphyrin contained within the cell, probably do not occur among the majority of parenchymal cells during in vivo photoirradiation.

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Antidote and Emergency Treatment
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

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Non-Human Toxicity Excerpts
/ALTERNATIVE and IN VITRO TESTS/ The interaction between anionic form of meso-tetrakis(4-carboxyphenyl) porphyrin (TCPP) and calf thymus deoxyribonucleic acid (CT DNA) is investigated by measuring UV-vis absorption, steady-state fluorescence, steady-state fluorescence anisotropy, time-resolved fluorescence, resonance light scattering (RLS), FT-IR and circular dichroism (CD) spectra along with the help of atomic force microscopy (AFM) under Tris-Borate-EDTA (TBE) buffer solution of pH 8.3. The static mode of fluorescence quenching of porphyrin by calf thymus deoxyribonucleic acid indicates the formation of a ground-state complex. The formation of ground-state complex is a spontaneous molecular interaction procedure in which outside groove binding through hydrogen bond or van der Waals force plays a major role. For biomedical application this investigation is very important as here TCPP, i.e. the anionic porphyrin does not bring any changes in the original structure of the CT DNA to selectively cleaving the nucleic acid to destroy the cancer or tumor cells whereas cationic porphyrin makes change in the protein structure significantly during the same process. PMID:20655240

/ALTERNATIVE and IN VITRO TESTS/ The photosensitizing effects of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, meso-tetra(p-carboxyphenyl)porphine, and meso-tetra(4-N-methylpyridyl)-porphine on ColE1 supercoiled DNA were studied using agarose gel electrophoresis. Photoinduced single- and double-strand breaks were observed to form under neutral conditions. Singlet oxygen was shown to predominate in the mechanism of the induction of these lesions in the case of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, and meso-tetra(p-carboxyphenyl)porphine and to play a significant role in the case of meso-tetra(4-N-methylpyridyl)porphine. The results suggest the possibility that the risk of photodynamic carcinogenesis may accompany photochemotherapy and fluorescence endoscopic procedures involving porphyrin photosensitizers. PMID:7020932

[1]. Removal of Cu(II) from water by tetrakis(4-carboxyphenyl) porphyrin-functionalized mesoporous silica. J Hazard Mater. 2011 Jan 30;185(2-3):1311-7.

Therapeutic Uses
/EXPL THER/ Particle size should be optimized to achieve targeted and extended drug delivery to the affected tissues. We describe here the effects of the mean particle size on the pharmacokinetics and photothrombic activity of meso-tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable nanoparticles based on poly(d,l-lactic acid). Four batches of nanoparticles with different mean sizes ranging from 121 to 343 nm, were prepared using the emulsification-diffusion technique. The extravasations of each TCPP-loaded nanoparticle formulation from blood vessels were measured, as well as the extent of photochemically induced vascular occlusion. These preclinical tests were carried out in the chorioallantoic membrane (CAM) of the chicken's embryo. Fluorescence microscopy showed that both the effective leakage of TCPP from the CAM blood vessels and its photothrombic efficiency were dependent on the size of the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the blood vessels and the surrounding tissue increased at the applied conditions, when the particle size decreased. This suggests that large nanoparticles are more rapidly eliminated from the bloodstream. In addition, after injection of a drug dose of 1 mg/kg body weight and a drug-light application interval of 1 min, irradiation with a fluence of 10 J/sq cm showed that the extent of vascular damage gradually decreased when the particle size increased. The highest photothrombic efficiency was observed when using the TCPP-loaded nanoparticles batch with a mean diameter of 121 nm. Thus, in this range of applied conditions, for the treatment of for instance a disease like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments suggest that the smallest nanoparticles may be considered as the optimal formulation since they exhibited the greatest extent of vascular thrombosis as well as the lowest extravasation. /TCPP nanoparticles/
/EXPL THER/ The role of the neoplastic cell in both porphyrin localization and the photochemotherapeutic response was investigated with the use of a series of tumor-localizing porphyrins and the L1210 tumor system. In vivo photoirradiation of DBA/2Ha mice bearing L1210 solid tumors and previously given injections of meso-tetra-(4-sulfonatophenyl)-porphine, meso-tetra-(4-carboxyphenyl)-porphine, or hematoporphyrin derivative (Hpd) indicated that all three chemicals elicited a photodynamic response resulting in necrosis of exposed tissue. Isolation of tumor cells from mice given injections of porphyrin with the use of mild mechanical means and physiologic conditions followed by in vitro photoirradiation of the cells under conditions established to optimize rapid cytocidal effects resulted in no appreciable cell death. A similar situation was noted with the use of spleen cells from mice given injections of Hpd, the spleen cells presumably containing substantial amounts of porphyrin. Both fluorescence microscopy and chemical extraction and quantitation of the porphyrins in the cells indicated that the inability to elicit a rapid cytocidal effect upon in vitro photoirradiation resulted from either the absence of or the presence of only very small amounts of porphyrin. These results indicate that in this particular tumor system the neoplastic cell per se plays only a minor role in porphyrin localization and, as a consequence, cannot be readily killed upon photoirradiation, suggesting that rapid cytocidal effects, due solely to porphyrin contained within the cell, probably do not occur among the majority of parenchymal cells during in vivo photoirradiation.
/EXPL THER/ We studied the uptake of meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles by SW480 cells and carried out a systematic investigation of the cellular internalization mechanism of TCPP nanoparticles, also studied the photocytotoxicity of TCPP nanoparticles. At first, meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles were prepared by the method of mixing solvent techniques. SW480 cellular uptakes of photosensitizers (TCPP nanoparticles, TCPP-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and free TCPP) were analyzed by the method of fluorospectrophotometry. Endocytosis mechanism investigation was carried out by preincubating SW480 cells at 4 degrees C, and preincubating SW480 cells with sucrose, K+-free buffer solution and filipin. Clathrin HC expression after incubating SW480 cells with these three photosensitizers was analyzed by methods of Western blot and RT-PCR. At last, we analyzed the photo-cytotoxicity after incubating SW480 cells with photosensitizers and receiving irradiation. SW480 cells showed rapid uptake (0.0083 fmoles TCPP/cell) of TCPP nanoparticles after 1h incubation. We also demonstrated that the uptake of TCPP nanoparticles by SW480 cells was a clathrin-mediated endocytosis pathway. As a result of rapid internalization of TCPP nanoparticles by SW480 cells, this special photosensitizer showed very high photocytotoxic effect on SW480 cells in vitro. The nano-sized photosensitizer with no matrix cover: TCPP nanoparticles, can produce higher photocytotoxicity than other photosensitizers (TCPP-loaded PLGA nanoparticles and free TCPP). The in vivo tumor growth inhibition experiment indicated that TCPP nanoparticles plus PDT treatment induced the most dramatic tumor-inhibiting efficacy in all TCPP treated groups. The results of this study suggest that TCPP nanoparticles represent a potential and powerful photodynamic therapy agent. /TCPP nanoparticles/
/EXPL THER/ Introduction: Early detection of lung cancer in high-risk individuals reduces mortality. Low-dose spiral computed tomography (LDCT) is the current standard but suffers from an exceedingly high false-positive rate (>96%) leading to unnecessary and potentially dangerous procedures. We, therefore, set out to develop a simple, noninvasive, and quantitative assay to detect lung cancer. Methods: This proof-of-concept study evaluated the sensitivity/specificity of the CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphenyl) porphyrin (TCPP)-labeled lung sputum samples and subjects' baseline characteristics were assessed for their predictive power by multivariable logistic regression. A receiver operating characteristic curve was constructed to evaluate the sensitivity/specificity of the CyPath assay. Results: RFCs were detectable in cancer subjects more often than in high-risk ones (p = 0.015), and their characteristics differed between cohorts. Two independent predictors of cancer were the mean of RFC average fluorescence intensity/area per subject (p < 0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall accuracy of 81% in the test population; false-positive rate of 40% and negative predictive value of 83%. Conclusions: The tetra (4-carboxyphenyl) porphyrin -based CyPath assay correctly classified study participants into cancer or high-risk cohorts with considerable accuracy. Optimizing sputum collection, sample reading, and refining the classifier should improve sensitivity and specificity. The CyPath assay thus has the potential to complement LDCT screening or serve as a stand-alone approach for early lung cancer detection.
/EXPL THER/ Athymic nude mice with subcutaneously xenotransplanted urothelial carcinoma received intravenously injections of the synthetic sensitizer meso-tetra (4-carboxyphenyl) porphyrin. Fluorescence at the tumors and the skin was excited using a Kr+ laser (407 nm) and was detected at 652 nm using a fiberoptical sensor in combination with an optical multichannel analyzer at different times after application of the sensitizer. Photodynamic treatment was carried out using an Ar+ laser pumped dye laser (650 nm; 100 mW/sq cm; 100 J/sq cm). The delay of tumor growth was determined in a follow-up period of four weeks and was correlated to the in vivo fluorescence measurements.

C48H30N4O8

790.79

790.206

14609-54-2

86278368

Dark blue to purple to black powder

1.5±0.1 g/cm3

> 300 °C

1.734

11.46

6

10

8

60

1310

0

O([H])C(C1C([H])=C([H])C(=C([H])C=1[H])C1C2C([H])=C([H])C(=C(C3C([H])=C([H])C(C(=O)O[H])=C([H])C=3[H])C3=C([H])C([H])=C(C(C4C([H])=C([H])C(C(=O)O[H])=C([H])C=4[H])=C4C([H])=C([H])C(C(C5C([H])=C([H])C(C(=O)O[H])=C([H])C=5[H])=C5C([H])=C([H])C=1N5[H])=N4)N3[H])N=2)=O |c:20,86,t:58,80|

HHDUMDVQUCBCEY-UHFFFAOYSA-N

InChI=1S/C48H30N4O8/c53-45(54)29-9-1-25(2-10-29)41-33-17-19-35(49-33)42(26-3-11-30(12-4-26)46(55)56)37-21-23-39(51-37)44(28-7-15-32(16-8-28)48(59)60)40-24-22-38(52-40)43(36-20-18-34(41)50-36)27-5-13-31(14-6-27)47(57)58/h1-24,49,52H,(H,53,54)(H,55,56)(H,57,58)(H,59,60)

4-[10,15,20-tris(4-carboxyphenyl)-21,23-dihydroporphyrin-5-yl]benzoic acid

14609-54-2; Tetracarboxyphenylporphine; CCRIS 8701; HSDB 8470; meso-Tetra-(4-carboxyphenyl)porphine; Benzoic acid, 4,4',4'',4'''-(21H,23H-porphine-5,10,15,20-tetrayl)tetrakis-; 4,4',4'',4'''-(Porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid); meso-Tetra(4-carboxyphenyl)porphine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 4 mg/mL (5.06 mM)

Solubility in Formulation 1: 2.5 mg/mL (3.16 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (3.16 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)