Novel nano-scaled Mn-metal-organic framework for enhancing photodynamic therapy through overcoming tumor hypoxia / 中国药科大学学报

@#A Mn-clusters-porphyrin metal-organic framework nanosheet(nMn-MOF)was synthesized by coordination chelation to enhance photodynamic therapy. The nanosheet was characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Oxygen sensor and ICG were used to investigate the production of oxygen and the singlet oxygen(1O2)generation. The cytotoxicity of the nanosheet against tumor cells were detected by CCK-8 assay, and the anti-hypoxia and oxygen-generation ability of nanosheets were investigated by fluorescence staining assay. The results indicated that this nanosheet could catalyze the intracellular H2O2 into O2, which overcame the tumor hypoxia. Furthermore, the generated oxygen was converted to cytotoxic 1O2 under the near infrared light irradiation, thereby enhancing photodynamic therapy.

In vitro photodynamic antibacterial activity of cationic porphyrin derivative / 国际生物医学工程杂志

Objective To investigate susceptibility and antibacterial activity of cationic porphyfin derivative mediated photodynamic antimicrobial chemotherapy (CPD-PACT) against Pseudomonas aeruginosa,to provide experimental evidence for its high efficiency antibacterial activity.Methods The impacts of culture environments on minimum inhibitory concentration (MIC) were measured by double dilution method.The formation of inhibition zone was determined by diffusion plate method.The postantibiotic effect was analyzed by colony forming units.The viability and morphology of Pseudomonas aeruginosa were observed by confocal laser scanning microscopy (CLSM).Results The inoculum size of bacterial had a certain effect on the MIC.The MIC values increased as the pH of medium rose.When the calf serum content of culture medium increased,the MIC rose in light reaction and dropped in dark reaction.The diameter of inhibition zone mainly depended on the laser energy density,but not the concentration of photosensitizer.Though CPD possessed strong antimicrobial activity and persistent suppression on bacterial growth,the surviving Pseudomonas aeruginosa would soon continue to proliferate after PACT.The fluorescence images captured by CLSM showed that CPD-PACT could destroy the membrane integrity,leak the cytoplasmic component,decrease the bacterial activity and finally lead Pseudomonas aeruginosa to death.Conclusions CPD has strong inhibitory activity and obvious postantibiotic effect on Pseudomonas aeruginosa,which is suitable to be developed as an drug candidate for PACT.

Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles.

Antinociceptive activity of Sargassum polyceratium and the isolation of its chemical components

Abstract Marine algae have been the focus of important studies over the past fifty years, with a considerable number of components important to chemists and taxonomists having been isolated and characterized. The scientific data available on Sargassum polyceratium are extremely limited. The objective of the present study was to evaluate the antinociceptive activity of an ethanol extract of S. polyceratium and to isolate its components. Intraperitoneal treatment with ethanol extract of S. polyceratium reduced the number of acetic acid-induced writhes and the amount of time spent in paw-licking in the second phase of the formalin test. Ethanol extract of S. polyceratium also reduced the amount of time spent in paw-licking in the glutamate test; however, there was no difference in the reaction time in the hot plate test at any of the doses tested. The chemical components isolated from ethanol extract of S. polyceratium were identified using one- and two-dimensional spectroscopic methods such as infrared spectroscopy, mass spectrometry and 1H and 13C nuclear magnetic resonance spectroscopy. The analytical results were also compared with data obtained in the literature. The following porphyrin derivatives were isolated from S. polyceratium: 132-hydroxy-(132-R)-pheophytin-a, 132-hydroxy-(132-S)-pheophytin-a, pheophytin-a, and the steroid fucosterol. The present results indicate that the ethanol extract of S. polyceratium has antinociceptive activity. In addition, four new substances were isolated from the species evaluated.

New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity

This work studied the synthesis of 5,10,15-tris(4-aminophenyl)-20-(N,N-dialkyl/diaryl-N-phenylurea) porphyrins (P1-P4 with alkyl or aryl groups of Ph, iPr, Et and Me, respectively) and also the preparation of their manganese (III) and cobalt (II) complexes (MnP and CoP). The P1-P4 ligands were characterized by different spectroscopic techniques (1H NMR, FTIR, UV-Vis) and elemental analysis, and metalated with Mn and Co acetate salts. The antibacterial and antifungal activities of these compounds in vitro were investigated by agar-disc diffusion method against Escherichia coli (-), Pseudomonas aeruginosa (-), Staphylococcus aureus (+), Bacillus subtilis (+) and Aspergillus oryzae and Candida albicans. Results showed that antibacterial and antifungal activity of the test samples increased with increase of their concentrations and the highest activity was obtained when the concentration of porphyrin compounds was 100 µg/mL. The activity for the porphyrin ligands depended on the nature of the urea derivative substituents and increased in the order P1 > P2 > P3 >P4, which was consistent with the order of their liposolubility. MnP and CoP complexes exhibited much higher antibacterial and antifungal activity than P1-P4 ligands. Further, the growth inhibitory effects of these compounds was generally in the order CoP complexes > MnP complexes > P1-P4 ligands. Among these porphyrin compounds, CoP1 displayed the highest antibacterial and antifungal activity, especially with a concentration of 100 µg/mL, against all the four tested bacteria and two fungi, and therefore it could be potential to be used as drug.

Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent / Produção, controle de qualidade, avaliação de biodistribuição e avaliação da dose preliminar de [177Lu] -tetra complexo fenil porfirina como um possível agente terapêutico

Due to interesting therapeutic properties of ¹⁷⁷Lu and tumor avidity of tetraphenyl porphyrins (TPPs), ¹⁷⁷Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. ¹⁷⁷Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu₂O₃sample with thermal neutron flux of 4 × 10¹³ n.cm^-2.s^-1. Tetraphenyl porphyrin was synthetized and labeled with ¹⁷⁷Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC) method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD) method. A detailed comparative pharmacokinetic study was performed for ¹⁷⁷Lu cation and [¹⁷⁷Lu]-TPP. The complex was prepared with a radiochemical purity: >97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [¹⁷⁷Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human...

Devido às propriedades interessantes do ¹⁷⁷Lu e da avidez tumoral das tetrafenil porfirinas (TPP), desenvolveu-se a ¹⁷⁷Lu-tetrafenil porfirina como composto terapêutico potencial. ¹⁷⁷Lu de atividade específica de 2,6-3 GBq/mg foi obtido por irradiação de amostra de Lu₂O₃ com fluxo térmico de nêutrons de 4 × 10¹³ n.cm^-2.s^-1. Sintetizou-se a tetrafenil porfirina e marcou-se com ¹⁷⁷Lu. A pureza radioquímica do complexo foi estudada usando método de Cromatografia Instantânea de Camada Delgada ( ITLC). A estabilidade do complexo foi checada na formulação final e no ser humano por 48 h. A biodistribuição do composto marcado em órgãos vitais de ratos do tipo selvagem foi estudada por mais de 7 dias. A dose absorvida para cada órgão humano foi calculada pelo método da Dose Médica de Radiação Interna (MIRD). Estudo farmacocinético comparativo detalhado foi efetuado para o cátion ¹⁷⁷Lu e para o [¹⁷⁷Lu]-TPP. O complexo foi preparado com pureza radioquímica >97±1% e atividade específica de 970-1000 MBq/mmol. Os dados de biodistribuição e os resultados dosimétricos mostraram que todos os tecidos receberam uma dose absorvida aproximadamente insignificante devido à rápida excreção do complexo pelo trato urinário. O [¹⁷⁷Lu]-TPP pode ser um agente interessante de direcionamento do tumor devido à baixa captação pelo fígado e pela dose bem baixa absorvida, de, aproximadamente, 0,036 do corpo humano total...

Porfiria y gestación: a propósito de un caso / Porphyria and pregnancy: case report

The porphyrias are a group of diseases caused by a deficiency of enzymes responsible for the synthesis of heme, that can lead to severe disease that requires early diagnosis to avoid complications. The frequency of the disease is low and its association with pregnancy unusual, but it is a good time for patients carrying develop the disease or suffer an exacerbation of the same, hence the vital importance of prophylaxis of the factors risk.

Las porfirias son un grupo de enfermedades producidas por un déficit de las enzimas encargadas de la síntesis del hemo, que pueden dar lugar a un cuadro clínico grave que requiere un diagnóstico precoz para evitar complicaciones. La frecuencia de la enfermedad es baja y su asociación con el embarazo inusual, pero es un buen momento para que las pacientes portadoras desarrollen la enfermedad o sufran una exacerbación de la misma, de ahí la importancia vital de la profilaxis de los factores de riesgo.

Synthesis of glucose conjugated porphyrins / 国际生物医学工程杂志

Objective Porphyrin, when conjugated with glucose, will be improved in its water solubility and biocompatibility. Methods In this paper, based on 4- (2, 3, 4, 6-tetra-O-acetyl-β-D-glucosyloxy)benzaldehyde and pyrrole, glucose conjugated porphyrins were synthesized in an optimized process, while porphyrin dimer was synthesized by the Ag-promoted coupling reaction of glycoconjugated porphyrin monomer.Results The compounds were characterized by 1H NMR and MS. Results showed that porphyrin conjugated with two glucose units has slight water solubility, while porphyrin conjugated with three or four glucose units has excellent water solubility. Conclusion Glucoconjugation improves water-solubility of porphyrins, which will enlarge its application in biological fields.

Photodynamic efficiency of new porphyrin-typed drug on HGC27 and MGC803 cells / 国际生物医学工程杂志

Objective To explore photodynamic therapeutic efficiency and related mechanisms of a new porphyrin-typed photodynamic therapy (PDT) drug synthesized in our lab on HGC27 and MGC803 cells.Methods Two different kinds of gastric cancer cells, HGC27 and MGC803, were chosen as cell lines to evaluate the PDT efficiency of new porphyrin-typed PDT drug based upon four group experiments: control (no drug, no light) group, drug treated group (only drug, no light), light treated group (no drug, only light) and experiment group (with drug and light at the same time). Bleaching method was used to evaluate the photostability of new porphyrin-typed PDT drug upon repititive illumination. MTT assay was carried out to test the survival rate of tumor cells after PDT. Cofocal laser scanning microscope (CLSM) was applied to observe subcellular localization of drug in HGC27 and MGC803 cells (mitochondria and lysosome). Results New porphyrin-typed PDT drug has good stability to light, no toxicity on HGC27 and MGC803 cells without light (P>0.05), while intense lethal effect was observed upon light illumination (P<0.05). The peak efficacy appeared when concentration is 3.12 μmol/L for both HGC27 and MGC803 cells and the new porphyrin-typed PDT drug localizes in lysosome other than traditional mitochondrion. Conclusion New porphyrin-typed PDT drug is a good photodynamic therapeutic sensitizer for HGC27 and MGC803 tumor cells.

Study on porphyrin and related metal-porphyrin recognition of carbohydrate / 国际生物医学工程杂志

Objective To study the molecular recognition of porphyrin compounds with carbohydrate molecular. Methods Fluorescent titration method was developed to explore the porphyrin and its metal porphyrin compounds interaction with carbohydrate compounds. Results The binding constants indicated that porphyrin and its metal compounds involved in this experiment could recognize carbohydrate compounds respectively, and interaction with lactose is stronger than glucose; Comparison with free porphyrin, metal ion Zn~(2+) and Fe~(3+) in the core of porphyrin compounds could enhance the binding capability with carbohydrate. Conclusion Porphyrin compounds has selective molecular recognition abilityto sugar molecular.

The effect of bamboo shoots extract compound on the treatment of hemorrhagic anemia / 中国输血杂志

Objective To observe of therapeutic effect of bamboo shoots extract compound on the treatment of hemorrhagic anemia.Method The glucose,total protein,amino acids,trace and macro elements in bamboo shoots extract were determined.Through the performance of angular vein bloodletting,a hemorrhagic anemia rat model was set up.Two therapy groups received the intragastric administration of compound Ⅰ(0.15% iron porphyrin and 10% honey) and compound Ⅱ(70% bamboo shoots extract,0.15% iron porphyrin and 10% honey),respectively.And the control group only received the de-ionized water of the same dose.The blood samples,collected via tail vein in 0,18,42,67 and 90h after the administration,were detected for hemoglobin,red blood cell and hematocrit.And the acute toxicity test was also conducted.Result Compound Ⅱ,which contained the Bamboo shoots extract that was rich in glucose,amino acids,amino,and trace and macro elements,had a better efficacy in treating hemorrhagic anemia of rats than the Compound Ⅰ.And the result of acute toxicity was normal. Conclusion Bamboo shoots extract compound could promote the recovery of hemorrhagic anemia.

Electroanalytical method for TPPS4 ,the interaction of TPPS4 with BSA and the influence of CDs on it by fluorescence spectroscopy / 药学学报

Aim To establish a simple, rapid and accurate electroanalytical method for water soluble porphyrin meso-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS4);to clarify the reaction between water soluble porphyrins and bovine serum albumin (BSA);and to determine the interaction of TPPS4 with BSA in the absence of presence of cyclodextrins (CDs) , separately. Methods Three methods including LSV,UV spectroscopy and fluorescence spectroscopy bad been employed to the relevant experiments. The way of employing three methods at the same time could make the experiment results more reliable. Results In the supporting electrolyte of NaH2 PO4-Na2 HPO4 ( pH 7. 18 ), a sensitive reduction peak of TPPS4 was found by linear sweep voltammetry (LSV), the peak potential (Ep) was-0. 70 V (vs SCE). The relationship between the second derivative peak of LSV (ip") and the concentration of TPPS4 was linear from 1.0 × 10-7mol·L-1 to 1.0 × 10-5mol· L-1,the square of correlation coefficients (r2) were 0. 998 3 and 0. 999 3, respectively. The relative standard deviation (RSD) was 0. 56% ( n = 5 ). The mean recovery of TPPS4 was 99.59％. In NH4C1-NH3· H2O buffers (pH 9.05), it was proved that BSA and TPPS4 could interact with each other and form 1:1 TPPS4-BSA supramolecular system. Moreover, the interaction between TPPS4 and BSA had been investigated by adding cyclodextrins (CDs). The interaction of TPPS4 with BSA was facilitated both by hydroxypropyl-β-CD (HP-3-CD) and sulforbutylether-β-CD (SBE-3-CD). Conclusion An electroanalytical method for TPPS4 has been established by LSV. The porphyrin drugs included by CDs could react with protein existing inside the human body easier. The consequences of this article also show that CDs will play important role in controlling and releasing the porphyrin drugs.

A Case of Pseudoporphyria / 대한피부과학회지

Pseudoporphyria is a generic term that is used to describe photoaggravated bullous dermatoses associated with multiple iatrogenic causes, including medications and dialysis. The bullous lesions of pseudoporphyria are similar to those of porphyria cutanea tarda, both clinically and histologically, but they occur in the absence of the abnormally high levels of porphyrins which are found in true porphyrias. Treatment entails discontinuation of suspected agents and sun protection, especially against UVA wavelengths. We report a case of pseudoporphyria in a 28-year-old male who had erythematous crusted erosions, vesicles and hyperpigmented macules on his face and both forearms. A biopsy from his Lt. forearm revealed subepidermal bullaes with festooning of dermal papillae, and mild lymphocytic perivascular infiltrations. However laboratory tests for porphyrin were negative in his urine, blood and stool.

Design,Synthesis and Biological Activity of Cationic Porphyrins Bearing Mixed 3-Quinolyl and 4-Pyridyl Meso Groups / 中国药科大学学报

AIM:To search for the potent telomerase inhibitors with structures of cationic porphyrins to improve the interactions between G-quadruplex and porphyrins by systematically varying the meso substituents.METHODS:Porphyrins bearing mixed 3-quinolyl/4-pyridyl meso groups were synthesized using the Adler-Longo method by condensation of aldehydes with pyrrole,and then followed by methylation and ion exchange.The compounds were tested for the telomerase inhibitory activity and c-Myc inhibitory activity.RESULTS:All compounds were found to be potent and approximately equivalent in terms of their ability to inhibit the action of telomerase in a cell-free assay.Compound 4 had the best inhibitory activity on c-Myc.CONCLUSION:Cationic porphyrins would be the potential anticancer candidates.

Expression of Apurinic/apyrimidinic Endonuclease and Neuronal Apoptosis in the Striatum after Treatment of 3-Nitropropionic Acid in Mice

BACKGROUND: 3-Nitroporpionic acid (3-NP) is an irreVersible inhibitor of succinate dehydrogenase in mitochondria and can induce apoptosis-like cell death in the striatum. It has been reported that oxidative stress plays a role in the 3-NP induced neuronal damage. 3-NP induced striatal damage is implicated in the pathogenesis of several neurological diseases, such as chronic neurodegenerative diseases and stroke. The DNA repair enzyme, apurinic/apyrimidinic endonuclease (APE), is a multifunctional protein in the DNA base excision repair (BER) pathway. To clarify the relationship between APE and neuronal cell death associated with the apoptosis in the striatum was induced by 3-NP in vivo. METHODS: After intra-striatal injection of 3-NP, expression of the APE protein and mRNA were evaluated by Western blot, immunohistochemistry, RT-PCR and DNA fragmentation patterns. Oxidative DNA damage was investigated by detection of oxidized DNA, AP site and superoxide. RESULTS: Expression levels of APE was rapidly reduced as early as 1hr after injection of 3-NP. DNA fragmentation was observed 24 hours after 3-NP treatment but not 4 hours. APE gene expression was increased to 1hr after 3-NP treatment. The number of AP sites were reduced and the reduction of APE proteins were blocked by a superoxide scavenger, MnTBAP-treatment. CONCLUSIONS: These results suggest that the reduction of APE is the preceding event of DNA fragmentation that causes apoptosis and a decrease of APE may be induced by ROS after 3-NP treatment.

Preparation and Bioactivity of Cationic Porphyrins Bearing Mixed 3-quinolyl and 3-pyridyl Meso Groups / 中国药科大学学报

AIM: To search for the potent telomerase inhibitors with structures of cationic porphyrins to improve the interactions between G-quadruplex and porphyrins by systematically varying the meso substituents. METHOD: Porphyrins bearing mixed 3-quinolyl/3-pyridyl meso groups were synthesized using the Adler-Longo method by condensation of aldehydes with pyrrole, followed by methylation and ion-exchange. The compounds were tested for the telomerase inhibitory activity and c-Myc inhibitory activity. RESULT: All compounds were found to be potent and approximately equivalent in terms of their ability to inhibit the action of telomerase in a cell-free assay. Compound 4 had the best inhibitory activity on c-Myc.

Urinary Porphyrins in Patients with Endemic Chronic Arsenic Poisoning Caused by Burning Coal in China

Objective: To evaluate the effect of arsenic (As) on the porphyrin biosynthetic pathway, urine samples from patients with endemic chronic arsenic poisoning were examined.Subjects and Methods: The subjects were 16 patients, who had been exposed to As from burning coal for 8 to 25 years, and-16 controls living in the same region in Guizhou Province in southwest China. Concentrations of urinary As, porphyrins and ALA were determined by induced coupled plasma mass spectrometry (ICP-MS), high performance liquid chromatography (HPLC) with a reversed-phase column and fluorescence detector, and colorimetric spectrophotometry, respectively.Results: Concentrations of As in patients and controls, 184.40 ± 200.04 and 86.82 ± 64.20 μ g/g creatinine (mean ± SD) respectively, were significantly different (p<0.05). The concentrations of various kinds of urinary porphyrins, including isomers I and III of coproporphyrin and pentacarboxylporphyrin, were determined. Positive correlations were observed between As and porphyrins (e.g. total porphyrins, hexacarboxylporphyrin and coproporphyrin III) or between As and ALA in male and female patients. However, porphyrin and ALA concentrations were not significantly different between the patients and the controls. Urinary porphyrin concentrations in females were higher than those in males.Conclusion: Exposure to As from burning coal may influence porphyrin biosynthesis.

Study on Removal of Nitrogen Oxides in Tobacco Smoke Main Stream / 环境与健康杂志

ve To explore the effective methods for removing the nitrogen oxides in tobacco smoke main stream. Methods Porphyrin and ferriporphyrin were added into cigarette filter with doses of 2.0, 4.0 and 8.0 ?g per cigarette. The effectiveness of removal of nitrogen oxides in tobacco smoke main stream by porphyrin and ferripor-phyrin were determined by muriatic acid naphthaline-ethylene diamine spectrophotometry. Results The contents of nitrogen oxides in tobacco smoke main stream decreased with the increases of the contents of porphyrin and ferripor-phyrin added into the cigarette filters (porphyrin: r= -0.9943, P

Study on Preparation Process of Sodium Copper Porphyrin of Herba Ephedrae and Its Character / 中成药

Objective: To study the comprehensive utilization of Herba Ephedrae resources during the extraction process of ephedrin, that is the extracting of porphyrin compound.Methods: The process conditions for preparing sodium copper porphyrin were optimized by the two preparation processes and twice orthogonal tests. Results: Herba Ephedrae was powdered, steeped and boiled in alcohol, saponified, then extracted with xylene. The ephedrin was extracted from the upper layer of xylene extraction solution and sodium copper porphyrin was obtained from the lower layer by copper substituton, acidulation and alkalization. Conclusion: The optimum preparation process for producing sodium copper porphrin of Herba Ephedrae which is superior to porphyrin in the stability and colour is ascertained.

Extraction of Ephedrine and Prophyrin Copper Sodium of Ephedra / 中成药

Objective: To obtain ephedrine with porphyrin copper sodium from Herba Ephedrae. Methods: Application of ethanol to obtain ephedrine and porphyrin copper sodium from ephedra. The spoinfy reaction of porphyrin will take place, the integral ephedrine will turn into free ephedrine (dissolved in ether), when the liquor of ethanol of ethanol of ephedra are heated with NaOH. Using dimethylponyle to extract, the liquor will into two phases, one's (including sponify porphyrin) is water phase, the other's (including free ephedrine) is ether phase. Results: The yield proportion of ephedrine is 0.72%, and porphyrin copper sodium is 1.8%.Conclusion: It is practicable to extract porphyrin copper sodium with ephedrine from Herba Ephedrae.