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
To achieve drug targeting and prolong delivery to affected tissues, particle size should be optimized. This article describes the effect of average particle size on the pharmacokinetics and photothrombotic activity of mesoporous tetra(carboxyphenyl)porphyrin (TCPP), encapsulated in biodegradable poly(D,L-lactic acid) nanoparticles. Four batches of nanoparticles with average particle sizes ranging from 121 to 343 nm were prepared using an emulsion diffusion method. The exudation from blood vessels and the degree of photochemically induced vascular occlusion of each TCPP nanoparticle formulation were measured. These preclinical trials were conducted in chicken embryo chorioallantoic membrane (CAM). Fluorescence microscopy revealed that the effective leakage of TCPP from CAM vessels and its photothrombotic efficiency depended on the size of the nanoparticle drug carrier. Indeed, under experimental conditions, the fluorescence contrast of TCPP between the vessel and surrounding tissue increased as the particle size decreased. This suggests that larger nanoparticles are cleared from the blood more quickly. Furthermore, after injecting a drug dose of 1 mg/kg body weight and undergoing drug-phototherapy at a 1-minute interval, followed by irradiation with a light dose of 10 J/cm², the results showed that the degree of vascular damage gradually decreased with increasing particle size. The highest photothrombotic efficiency was observed when using TCPP-loaded nanoparticles with an average diameter of 121 nm. Therefore, under the applied conditions, such as the treatment of diseases related to age-related macular degeneration (AMD) and choroidal neovascularization (CNV), these experiments demonstrate that the smallest nanoparticles can be considered the optimal formulation because they exhibit the greatest degree of vascular thrombosis and the lowest extravasation. /TCPP Nanoparticles/
We investigated the uptake of mesoporous tetra(carboxyphenyl)porphyrin (TCPP) nanoparticles by SW480 cells and systematically studied the cellular internalization mechanism of TCPP nanoparticles, while also investigating the photocytotoxicity of TCPP nanoparticles. First, we prepared mesoporous tetra(carboxyphenyl)porphyrin (TCPP) nanoparticles using a mixed solvent method. The uptake of photosensitizers (TCPP nanoparticles, TCPP-loaded polylactic-co-glycolic acid (PLGA) nanoparticles, and free TCPP) by SW480 cells was analyzed using fluorescence spectrophotometry. The endocytosis mechanism was investigated by pre-incubating SW480 cells at 4°C, and by pre-incubating with sucrose, potassium-free buffer, and fenipin, respectively. The expression of clathrin heavy chain (HC) in SW480 cells after incubation with these three photosensitizers was analyzed using Western blot and RT-PCR. Finally, the photocytotoxicity of SW480 cells after incubation with the photosensitizers and subsequent irradiation was analyzed. The results showed that SW480 cells rapidly uptake TCPP nanoparticles (0.0083 fmol TCPP/cell) after 1 hour of incubation. We also confirmed that the uptake of TCPP nanoparticles by SW480 cells is achieved through a clathrin-mediated endocytosis pathway. Because SW480 cells can rapidly internalize TCPP nanoparticles, this special photosensitizer exhibits extremely high photocytotoxicity against SW480 cells in vitro. This matrix-free nanoscale photosensitizer—TCPP nanoparticles—exhibits higher photocytotoxicity than other photosensitizers (TCPP-loaded PLGA nanoparticles and free TCPP). In vivo tumor growth inhibition experiments showed that among all TCPP treatment groups, TCPP nanoparticles combined with photodynamic therapy (PDT) had the most significant tumor-suppressive effect. These results indicate that TCPP nanoparticles are a potential and highly effective photodynamic therapy drug. /TCPP Nanoparticles/
Athymic nude mice with subcutaneous xenograft urothelial carcinoma received intravenous injection of the synthetic photosensitizer mesoporous tetra(4-carboxyphenyl)porphyrin. Fluorescence in the tumor and skin was excited using a Kr+ laser (407 nm), and fluorescence was detected at 652 nm at different time points after photosensitizer injection using a fiber optic sensor combined with an optical multichannel analyzer. Photodynamic therapy was performed using an Ar+ laser-pumped dye laser (650 nm; 100 mW/cm²; 100 J/cm²). Tumor growth delay was assessed during a four-week follow-up period and correlated with in vivo fluorescence measurements. Mesoporous tetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP readily couples with amine compounds, facilitating the attachment of functional groups. This study synthesized and evaluated tetravalent lysine-coupled mTCPP to explore its potential applications in targeted imaging and photodynamic therapy. We first coupled Fmoc-protected D-lysine or L-lysine to the ε-amino group of mTCPP via an amide coupling reaction, followed by Fmoc deprotection. The resulting compound exhibited poor solubility in aqueous solution but could be dissolved with the aid of surfactants such as bile acids. The L-amino acid transporter (LAT1) can take up a variety of neutral L-amino acids. In vitro U87 cell studies showed that hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors were nonspecifically taken up, while D-lysine or L-lysine-conjugated mTCPPs were not. Similarly, only the Fmoc-protected compounds induced significant phototoxicity in cells after blue light irradiation and incubation. These results do not provide evidence that lysine-mTCPPs specifically target cancer cells. However, they do highlight mTCPPs as a convenient and readily available framework for evaluating the molecular targeting of photosensitizers. /Lysine-conjugated mTCPP/

Toxicity Summary
Identification and Uses: Tetracarboxyphenylporphyrin (TCPP) is a deep blue to purple to black powder. TCPP is a potent photosensitizer that is activated by visible light. It has been used as a research chemical, chemical intermediate, and porphyrin dye. It has been used in animal cell models for photodynamic therapy testing of cancer and as a non-invasive diagnostic assay for lung cancer patients. Human Studies: No data available. Animal Studies: The photosensitizing effect of TCPP on ColE1 supercoiled DNA was studied using agarose gel electrophoresis. Photoinduced single-strand and double-strand breaks were observed under neutral conditions. Interactions The role of tumor cells in porphyrin localization and photochemotherapy responses was investigated using a series of tumor-localizing porphyrins and the L1210 tumor system. DBA/2Ha mice carrying L1210 solid tumors were subjected to in vivo photoirradiation. These mice had previously been injected with meso-tetra-(4-sulfonic acid phenyl)porphyrin, meso-tetra-(4-carboxyphenyl)porphyrin, or a hematoporphyrin derivative (Hpd). Results showed that all three chemicals induced a photodynamic response, leading to necrosis of the exposed tissue. Tumor cells were isolated from porphyrin-injected mice using mild mechanical methods and physiological conditions. No significant cell death was observed under in vitro photoirradiation conditions optimized for rapid cytotoxicity. A similar outcome was observed using spleen cells from Hpd-injected mice, which likely contained high levels of porphyrin. Fluorescence microscopy and chemical extraction and quantification of intracellular porphyrins indicated that the failure of in vitro photoirradiation to rapidly induce cytotoxicity was due to the absence or extremely low concentration of porphyrins. These results indicate that in this specific tumor system, tumor cells themselves play only a minor role in porphyrin localization and are therefore not easily killed by light. This suggests that the rapid cytotoxic effect caused solely by intracellular porphyrins during in vivo light exposure may not occur in most parenchymal cells.

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Antidotes and First Aid Measures
/SRP:/ Immediate First Aid Measures: Ensure adequate decontamination has been performed. If the patient stops breathing, begin artificial respiration immediately, preferably using a ventilator on demand, bag-valve-mask, or simple breathing mask (if trained). Perform cardiopulmonary resuscitation if necessary. Immediately flush contaminated eyes with running water. Do not induce vomiting. If vomiting occurs, tilt the patient forward or place them in the left lateral decubitus position (head down if possible) to maintain an open airway and prevent aspiration. Keep the patient calm and maintain normal body temperature. Seek immediate medical attention. /Class A and Class B Poisons/
/SRP:/ Basic Treatment: Establish an open airway (using an oropharyngeal or nasopharyngeal airway if necessary). Suction if necessary. Observe for signs of respiratory failure and provide assisted ventilation if necessary. Administer oxygen via a non-invasive mask at a flow rate of 10 to 15 liters per minute. Monitor for pulmonary edema and treat as needed… Monitor for shock and treat as needed… Anticipate seizures and treat as needed… If eyes become contaminated, flush immediately with water. During transport, continuously flush each eye with 0.9% saline… Do not use emetics. In case of ingestion, rinse mouth and dilute with 5 mL/kg to 200 mL of water, provided the patient is able to swallow, has a strong gag reflex, and does not drool… After decontamination, cover skin burns with a dry, sterile dressing… /Class A and Class B Poisons/
/SRP:/ Advanced Treatment: For patients with impaired consciousness, severe pulmonary edema, or severe respiratory distress, consider oropharyngeal or nasopharyngeal endotracheal intubation to control the airway. Positive pressure ventilation via bag-valve-mask may be effective. Consider medical treatment for pulmonary edema… Consider using a beta-agonist (such as salbutamol) to treat severe bronchospasm… Monitor heart rhythm and treat arrhythmias if necessary… Start intravenous infusion of 5% glucose solution (D5W TKO)/SRP: “Keep patent,” minimum flow rate/. If signs of hypovolemia appear, use 0.9% normal saline (NS) or lactated Ringer's solution (LR). Use caution with fluid administration for hypotension accompanied by signs of hypovolemia. Watch for signs of fluid overdose… Treat seizures with diazepam (Valium) or lorazepam (Ativa)… Use promecaine hydrochloride to assist eye irrigation… /Toxins A and B/

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Non-human Toxicity Excerpt
/Alternatives and In Vitro Tests/ The interaction between the meso-tetra(4-carboxyphenyl)porphyrin (TCPP) anionic form and calf thymus DNA (CTDNA) was investigated in a Tris-borate-EDTA (TBE) buffer solution at pH 8.3 by measuring UV-Vis absorption spectroscopy, steady-state fluorescence spectroscopy, steady-state fluorescence anisotropy spectroscopy, time-resolved fluorescence spectroscopy, resonance light scattering (RLS), Fourier transform infrared spectroscopy (FT-IR), and circular dichroism spectroscopy (CD), and with the aid of atomic force microscopy (AFM). Static fluorescence quenching of CTDNA by CTDNA indicated the formation of a ground-state complex. The formation of the ground-state complex is a spontaneous molecular interaction process in which outer groove bonding via hydrogen bonds or van der Waals forces plays a major role. This research is significant for biomedical applications because anionic porphyrin TCPP does not alter the original structure of CT DNA, thus selectively cleaving nucleic acids to destroy cancer or tumor cells, while cationic porphyrins significantly alter protein structure in the same process. PMID:20655240
/Alternatives and In Vitro Assays/ This study investigated the photosensitization of ColE1 supercoiled DNA by hematoporphyrin derivatives, namely meso-tetra(p-sulfonylphenyl)porphyrin, meso-tetra(p-carboxyphenyl)porphyrin, and meso-tetra(4-N-methylpyridyl)porphyrin, using agarose gel electrophoresis. Photoinduced single-strand and double-strand breaks were observed under neutral conditions. Singlet oxygen dominates the carcinogenic mechanisms of hematoporphyrin derivatives, such as meta-tetra(p-sulfonic acid phenyl)porphyrin and meta-tetra(p-carboxyphenyl)porphyrin, and plays an important role in the carcinogenic mechanism of meta-tetra(4-N-methylpyridyl)porphyrin. These results suggest that photochemotherapy and fluorescence endoscopy using porphyrin photosensitizers may carry a risk of photodynamic carcinogenesis. 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
Particle size should be optimized to achieve targeted and prolonged drug delivery to affected tissues. This article describes the effect of average particle size on the pharmacokinetics and photothrombotic activity of mesoporous tetra(carboxyphenyl)porphyrin (TCPP), encapsulated in biodegradable poly(D,L-lactic acid) nanoparticles. Four batches of nanoparticles with average particle sizes ranging from 121 to 343 nm were prepared using an emulsion diffusion method. The leakage of each TCPP nanoparticle formulation from blood vessels and the degree of photochemically induced vascular occlusion were measured. These preclinical trials were conducted in chicken embryo chorioallantoic membrane (CAM). Fluorescence microscopy revealed that the effective leakage of TCPP from CAM vessels and its photothrombotic efficiency depended on the size of the nanoparticle drug carrier. Indeed, under experimental conditions, the fluorescence contrast of TCPP between the vessel and surrounding tissue increased as the particle size decreased. This suggests that larger nanoparticles are cleared from the blood more quickly. Furthermore, after injecting a drug dose of 1 mg/kg body weight and undergoing drug-phototherapy at a 1-minute interval, followed by irradiation with a light dose of 10 J/cm², the results showed that the degree of vascular damage gradually decreased with increasing particle size. The highest photothrombosis efficiency was observed when using TCPP-loaded nanoparticles with an average diameter of 121 nm. Therefore, in this application range, such as the treatment of diseases like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments demonstrate that the smallest nanoparticles can be considered the optimal formulation because they exhibit the greatest degree of vascular thrombosis and the lowest extravasation. /TCPP Nanoparticles/
/EXPL THER/ This study explored the role of tumor cells in porphyrin localization and photochemotherapy responses using a series of tumor-localizing porphyrins and the L1210 tumor system. DBA/2Ha mice carrying L1210 solid tumors were subjected to in vivo photoirradiation. These mice had previously been injected with meso-tetra-(4-sulfonic acid phenyl)porphyrin, meso-tetra-(4-carboxyphenyl)porphyrin, or a hematoporphyrin derivative (Hpd). Results showed that all three chemicals induced a photodynamic response, leading to necrosis of the exposed tissue. Tumor cells were isolated from porphyrin-injected mice using mild mechanical methods and physiological conditions. No significant cell death was observed under in vitro photoirradiation conditions optimized for rapid cytotoxicity. A similar outcome was observed using spleen cells from Hpd-injected mice, which likely contained high levels of porphyrin. Fluorescence microscopy and chemical extraction and quantification of intracellular porphyrins indicated that the failure of in vitro photoirradiation to rapidly induce cell death was due to extremely low or complete absence of intracellular porphyrins. These results indicate that in this specific tumor system, tumor cells themselves play only a minor role in porphyrin localization and are therefore not easily killed under light. This suggests that the rapid cell death effect caused solely by intracellular porphyrins during in vivo phototherapy may not occur in most parenchymal cells. We investigated the uptake of mesoporous tetra(carboxyphenyl)porphyrin (TCPP) nanoparticles by SW480 cells and systematically studied the intracellular internalization mechanism of TCPP nanoparticles, as well as the photocytotoxicity of TCPP nanoparticles. First, mesoporous tetra(carboxyphenyl)porphyrin (TCPP) nanoparticles were prepared using a mixed solvent method. The uptake of photosensitizers (TCPP nanoparticles, TCPP-loaded polylactic-co-glycolic acid (PLGA) nanoparticles, and free TCPP) by SW480 cells was analyzed using fluorescence spectrophotometry. The endocytosis mechanism was investigated by pre-incubating SW480 cells at 4°C, and by pre-incubating them with sucrose, potassium-free buffer, and fenipin, respectively. Western blot and RT-PCR were used to analyze the expression of clathrin heavy chain (HC) in SW480 cells after incubation with these three photosensitizers. Finally, the photocytotoxicity of SW480 cells after incubation with the photosensitizer and subsequent light exposure was analyzed. SW480 cells rapidly uptake TCPP nanoparticles (0.0083 fmol TCPP/cell) after 1 hour of incubation. We also confirmed that the uptake of TCPP nanoparticles by SW480 cells is achieved through a clathrin-mediated endocytosis pathway. Due to the rapid internalization of TCPP nanoparticles by SW480 cells, this specific photosensitizer exhibits extremely high photocytotoxicity to SW480 cells in vitro. These matrix-free, nanoscale photosensitizers—TCPP nanoparticles—exhibit higher photocytotoxicity than other photosensitizers (TCPP-loaded PLGA nanoparticles and free TCPP). In vivo tumor growth inhibition experiments showed that among all TCPP treatment groups, the TCPP nanoparticle combined with photodynamic therapy (PDT) treatment group exhibited the most significant tumor inhibition effect. These results indicate that TCPP nanoparticles are a potential and effective photodynamic therapy drug. /TCPP Nanoparticles/
/EXPL THER/ Introduction: Early detection of lung cancer in high-risk populations can reduce mortality. Low-dose spiral CT (LDCT) is currently the standard examination method, but its false positive rate is extremely high (>96%), leading to unnecessary and potentially dangerous examinations. Therefore, we set out to develop a simple, non-invasive, and quantitative method for lung cancer detection. Methods: This proof-of-concept study evaluated the sensitivity and specificity of the CyPath early lung cancer detection method in high-risk control subjects (n = 102) and cancer subjects (n = 26) diagnosed by LDCT. We used multivariate logistic regression analysis to evaluate the predictive power of the fluorescence intensity parameter of red fluorescent cells (RFCs) in tetrate(4-carboxyphenyl)porphyrin (TCPP)-labeled lung sputum samples as well as the baseline characteristics of the participants. Furthermore, we plotted receiver operating characteristic (ROC) curves to assess the sensitivity and specificity of the CyPath detection method. Results: The frequency of RFC detection was higher in cancer patients than in high-risk individuals (p = 0.015), and there were differences in RFC characteristics between the two groups. Two independent predictors of cancer were the mean fluorescence intensity/area of RFCs per participant (p < 0.001) and years of smoking (p = 0.003). The CyPath-based classifier achieved an overall accuracy of 81%, a false positive rate of 40%, and a negative predictive value of 83% in the test population. Conclusion: The tetrate(4-carboxyphenyl)porphyrin-based CyPath detection method can correctly classify study participants into cancer patients or high-risk individuals with considerable accuracy. Optimizing sputum collection, sample interpretation, and improving the classifier are expected to enhance the sensitivity and specificity of the detection. Therefore, the CyPath detection method holds promise for complementing low-dose CT screening or serving as an independent method for early lung cancer detection.
/EXPL THER/ Athymic nude mice with subcutaneous xenograft urothelial carcinoma were intravenously injected with the synthetic sensitizer meta-tetra(4-carboxyphenyl)porphyrin. Fluorescence in the tumor and skin was excited using a Kr+ laser (407 nm), and fluorescence was detected at 652 nm at different time points after sensitizer injection using a fiber optic sensor combined with an optical multichannel analyzer. Photodynamic therapy was performed using an Ar+ laser-pumped dye laser (650 nm; 100 mW/cm²; 100 J/cm²). Tumor growth delay was assessed during a four-week follow-up period and correlated with in vivo fluorescence measurements.

C48H30N4O8

790.79

790.206

C, 72.91; H, 3.82; N, 7.09; O, 16.19

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.)