The Photodynamic Anti-Tumor Effects of New PPa-CDs Conjugate with pH Sensitivity and Improved Biocompatibility.

BACKGROUND: Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity. OBJECTIVE: This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT. METHODS: The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109). RESULTS: The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions. CONCLUSION: The dark toxicity, as well as hemocompatibility, was improved.

Incorporation of green emission polymer dots into pyropheophorbide-α enhance the PDT effect and biocompatibility.

BACKGROUND: A green emission up-conversion carbon-based polymer dots (CPDs) owned excellent photophysical properties and good solubility. Most photosensitizers (PS) are hydrophobic which limits their application in biomedicine. Herein we synthesized and integrated green emitting CPDs into pyropheophorbide-α (PPa) to improve the overall properties of the PS. MATERIAL AND METHODS: The nano-agent was incorporated through amide condensation and electrostatic interaction. The structure, size and morphology of the prepared conjugates were determined by FTIR, TEM, DLS, TGA, 1HNMR, Uv-vis, and fluorescence spectrophotometry. The dark and light toxicity, as well as cellular uptake, was also monitored on the human esophageal cancer cell line (Eca-109). RESULTS: Our results illustrate that the conjugation improved the PDT efficacy by increasing the ROS generation. The nano-hybrids showed pH sensitivity as well as good hemocompatibility as the hemolysis ratio was decreased when treated with nano-conjugates. PPa-CPD1 and PPa-CPD2 had the pH response and stronger ability to absorb light and produce fluorescence in an acidic environment (pH 4.0 and pH 5.0) The synthesized nano-hybrids doesnot affect the clotting time. An increase in the absorbance wavelengths was observed. The results of MTT assay showed that dark toxicity was reduced after conjugation. CONCLUSION: This CPDs-based drug enhanced tumor-inhibition efficiency as well as low dark toxicity in vitro, showing significant application potential for PDT-based treatment.

The improvement of biocompatibility by incorporating porphyrins into carbon dots with photodynamic effects and pH sensitivities.

Photodynamic therapy (PDT) is a promising new treatment for cancer; however, the hydrophobic interactions and poor solubility in water of photosensitizers limit the use in clinic. Nanoparticles especially carbon dots have attracted the attention of the world's scientists because of their unique properties such as good solubility and biocompatibility. In this paper, we integrated carbon dots with different porphyrins to improve the properties of porphyrins and evaluated their efficacy as PDT drugs. The spectroscopic characteristics of porphyrins nano-conjugates were studied. Singlet oxygen generation rate and the light- and dark-induced toxicity of the conjugates were studied. Our results showed that the covalent interaction between CDs and porphyrins has improved the biocompatibility. The synthesized conjugates also inherit the pH sensitivity of the carbon dots, while the conjugation also decreases the hemolysis ratio making them a promising candidate for PDT. The incorporation of carbon dots into porphyrins improved their biocompatibility by reducing toxicity.

Synthesis and in vitro PDT evaluation of red emission polymer dots (R-CPDs) and pyropheophorbide-α conjugates.

Carbon based polymer dots have piqued attention of researchers because of excellent biocompatibility, and good solubility. Most of the p-dots are able to generate ROS which is effective for photodynamic therapy for the treatment of cancer while some photosensitizers such as porphyrins possess some drawbacks such as hydrophobicity, and dark toxicity. Therefore in this study we conjugated red emission carbon based polymer with pyropheophorbide-α through amide condensation and π-π stacking. One pot synthesis of the conjugate was successfully achieved. Their photophysiological properties were studied and structures were characterized by FT-IR, TEM and 1HNMR. pH- sensitivity of the conjugates was confirmed using fluorescence and UV-vis spectroscopy. Photo toxicity and dark toxicity of the prepared conjugates were evaluated in human esophageal cancer cell line (Eca-109). Hemocompatibility of the synthesized conjugates was evaluated and proved that the conjugates are safe to use for the treatment of tumor. Our results showed the PS doped p-dots had less dark toxicity and increased light toxicity as well as ROS generation was high as compared to precursor drug. Therefore, incorporation of p-dots to porphyrin improved biocompatibility and enhanced the photodynamic effect.

Evaluation of antimicrobial photodynamic activities of 5-aminolevulinic acid derivatives.

BACKGROUND: Antibiotic resistance is increasing day by day, thereby increase the chances of more infections by resistant bacteria. In this situation, antimicrobial photodynamic therapy (aPDT) is gaining more attraction. OBJECTIVE: To evaluate the antimicrobial effect of ALA derivatives using photodynamic therapy. MATERIALS AND METHODS: In this study, we evaluated the aPDT effect of different derivatives of 5-ALA. In vivo and in vitro studies were performed to measure the antimicrobial activity. Different light doses and different concentrations of drugs were used to test anti-bacterial effect of drugs as well as to detect any physiological changes in animal model after the treatment. RESULTS: In vivo studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are potent photosensitizers. In vitro studies involved wound healing rate, body weight, and dietary intake were evaluated, and results showed that ALA, ALA-methyl ester, ALA-hexyl ester, and ALA-13A had good anti-bacterial effects, fast healing rate, and no effect on other physical parameters. CONCLUSION: Photodynamic therapy is increasingly used to treat different types of skin infections caused by bacterial strains. Our studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are promising photosensitizers for photodynamic therapy to inhibit the growth of resistant bacterial strains.

Synthesis and pharmacological evaluation of chlorin derivatives for photodynamic therapy of cholangiocarcinoma.

Photodynamic therapy (PDT) has been developed as a promising therapeutic method in cancer treatment. The discovery of effective photosensitizer, which is the key factor of PDT, is highly desired. This paper reports the synthesis of novel chlorin derivatives, 5,10,15,20-tetraphenyl-[2:3]-[(methoxycarbonyl, carboxy)methano] chlorin I and 5,10,15,20-tetraphenyl-[2:3]- {[methoxycarbonyl, (2-hydroxyethyl)amide]methano}chlorin II. Their structures were characterized with UV-vis, 1HNMR, 13CNMR and HRMS spectroscopies. Photophysical and photochemical experiments results showed that compound I and II had an absorption maximum around 650 nm, with molar extinction coefficients of 1 × 104 M-1 cm-1. They had strong fluorescence emission in 650-660 nm upon excitation with 419-422 nm light. ESR showed that singlet oxygen was produced upon irradiation of compounds with 650 nm light in the presence of molecular oxygen. The photo-bleaching test indicated that the structure of compounds was stable. These new compounds exhibit excellent anti-tumor effects and lower toxicity compared to m-THPC in vitro and in vivo. Compound I and II had high tumor selectivity, which could induced tumor cells shrinkage and necrosis under 650 nm laser irradiation. Flow cytometry revealed that the compounds might mediate PDT effect at late apoptotic phase. These results make these compound I and II promising candidates for future study in photo-diagnosis and photodynamic therapy of cholangiocarcinoma.

Environment and air pollution: health services bequeath to grotesque menace.

The objective of the study is to establish the link between air pollution, fossil fuel energy consumption, industrialization, alternative and nuclear energy, combustible renewable and wastes, urbanization, and resulting impact on health services in Malaysia. The study employed two-stage least square regression technique on the time series data from 1975 to 2012 to possibly minimize the problem of endogeniety in the health services model. The results in general show that air pollution and environmental indicators act as a strong contributor to influence Malaysian health services. Urbanization and nuclear energy consumption both significantly increases the life expectancy in Malaysia, while fertility rate decreases along with the increasing urbanization in a country. Fossil fuel energy consumption and industrialization both have an indirect relationship with the infant mortality rate, whereas, carbon dioxide emissions have a direct relationship with the sanitation facility in a country. The results conclude that balancing the air pollution, environment, and health services needs strong policy vistas on the end of the government officials.

Climate change and air pollution jointly creating nightmare for tourism industry.

The objective of the study is to examine the long-run and causal relationship between climate change (i.e., greenhouse gas emissions, hydrofluorocarbons, per fluorocarbons, and sulfur hexafluoride), air pollution (i.e., methane emissions, nitrous oxide emissions, and carbon dioxide emissions), and tourism development indicators (i.e., international tourism receipts, international tourism expenditures, natural resource depletion, and net forest depletion) in the World's largest regions. The aggregate data is used for robust analysis in the South Asia, the Middle East and North Africa, sub-Saharan Africa, and East Asia and the Pacific regions, over a period of 1975-2012. The results show that climatic factors and air pollution have a negative impact on tourism indicators in the form of deforestation and natural resource depletion. The impact is evident, as we have seen the systematic eroding of tourism industry, due to severe changes in climate and increasing strain of air pollution. There are several channels of cause-effect relationship between the climatic factors, air pollution, and tourism indicators in the World's region. The study confirms the unidirectional, bidirectional, and causality independent relationship between climatic factors, air pollution, and tourism indicators in the World. It is conclusive that tourism industry is facing all time bigger challenges of reduce investment, less resources, and minor importance from the government agencies because of the two broad challenges, i.e., climate change and air pollution, putting them in a dismal state.

The challenges of reducing greenhouse gas emissions and air pollution through energy sources: evidence from a panel of developed countries.

The objective of the study is to investigate the long-run relationship between climatic factors (i.e., greenhouse gas emissions, agricultural methane emissions, and industrial nitrous oxide emission), air pollution (i.e., carbon dioxide emissions), and energy sources (i.e., nuclear energy; oil, gas, and coal energy; and fossil fuel energy) in the panel of 35 developed countries (including EU-15, new EU member states, G-7, and other countries) over a period of 1975-2012. In order to achieve this objective, the present study uses sophisticated panel econometric techniques including panel cointegration, panel fully modified OLS (FMOLS), and dynamic OLS (DOLS). The results show that there is a long-run relationship between the variables. Nuclear energy reduces greenhouse gases and carbon emissions; however, the other emissions, i.e., agricultural methane emissions and industrial nitrous oxide, are still to increase during the study period. Electricity production from oil, gas, and coal sources increases the greenhouse gases and carbon emissions; however, the intensity to increase emissions is far less than the intensity to increase emissions through fossil fuel. Policies that reduce emissions of greenhouse gases can simultaneously alter emissions of conventional pollutants that have deleterious effects on human health and the environment.