Abstract
The impact of substituents on the photochemical and biological properties of tetraphenylporphyrin-based photosensitizers for photodynamic therapy of cancer (PDT) as well as photodynamic inactivation of microorganisms (PDI) was examined. Spectroscopic and physicochemical properties were related with therapeutic efficacy in PDT of cancer and PDI of microbial cells in vitro. Less polar halogenated, sulfonamide porphyrins were most readily taken up by cells compared to hydrophilic and anionic porphyrins. The uptake and PDT of a hydrophilic porphyrin was significantly enhanced with incorporation in polymeric micelles (Pluronic L121). Photodynamic inactivation studies were performed against Gram-positive (S. aureus, E. faecalis), Gram-negative bacteria (E. coli, P. aeruginosa, S. marcescens) and fungal yeast (C. albicans). We observed a 6 logs reduction of S. aureus after irradiation (10 J/cm2) in the presence of 20 μM of hydrophilic porphyrin, but this was not improved with incorporation in Pluronic L121. A 2-3 logs reduction was obtained for E. coli using similar doses, and a decrease of 3-4 logs was achieved for C. albicans. Rational substitution of tetraphenylporphyrins improves their photodynamic properties and informs on strategies to obtain photosensitizers for efficient PDT and PDI. However, the design of the photosensitizers must be accompanied by the development of tailored drug formulations.
MeSH terms
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Anti-Infective Agents / chemical synthesis
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Anti-Infective Agents / chemistry*
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Anti-Infective Agents / pharmacology
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Biological Transport
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Candida albicans / drug effects
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Candida albicans / growth & development
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Candida albicans / radiation effects
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Drug Design
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Enterococcus faecalis / drug effects
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Enterococcus faecalis / growth & development
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Enterococcus faecalis / radiation effects
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Escherichia coli / drug effects
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Escherichia coli / growth & development
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Escherichia coli / radiation effects
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Halogenation
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Humans
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Hydrophobic and Hydrophilic Interactions
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Light
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Micelles
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Microbial Sensitivity Tests
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Photochemotherapy / methods
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Photosensitizing Agents / chemical synthesis
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Photosensitizing Agents / chemistry*
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Photosensitizing Agents / pharmacology
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Poloxamer / chemistry
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Porphyrins / chemical synthesis
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Porphyrins / chemistry*
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Porphyrins / pharmacology
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / growth & development
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Pseudomonas aeruginosa / radiation effects
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Serratia marcescens / drug effects
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Serratia marcescens / growth & development
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Serratia marcescens / radiation effects
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / growth & development
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Staphylococcus aureus / radiation effects
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Structure-Activity Relationship
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Sulfonamides / chemistry
Substances
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Anti-Infective Agents
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Antineoplastic Agents
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Micelles
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Photosensitizing Agents
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Porphyrins
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Sulfonamides
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Poloxamer
Grants and funding
This work was funded by National Science Center (NCN), Poland within the Sonata Bis grant no 0085/IP3/2015/73 given to JMD.