Most cited article - PubMed ID 29355861
Antibacterial nitric oxide- and singlet oxygen-releasing polystyrene nanoparticles responsive to light and temperature triggers
Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time.
- Keywords
- cancer, nanoparticles, photodynamic effect,
- MeSH
- NIH 3T3 Cells MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents pharmacology therapeutic use MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Nanoparticles * MeSH
- Porphyrins * metabolism pharmacology MeSH
- Reactive Oxygen Species metabolism MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Photosensitizing Agents MeSH
- Porphyrins * MeSH
- Reactive Oxygen Species MeSH
Photodynamic inactivation (PDI) is a promising approach for the efficient killing of pathogenic microbes. In this study, the photodynamic effect of sulfonated polystyrene nanoparticles with encapsulated hydrophobic 5,10,15,20-tetraphenylporphyrin (TPP-NP) photosensitizers on Gram-positive (including multi-resistant) and Gram-negative bacterial strains was investigated. The cell viability was determined by the colony forming unit method. The results showed no dark cytotoxicity but high phototoxicity within the tested conditions. Gram-positive bacteria were more sensitive to TPP-NPs than Gram-negative bacteria. Atomic force microscopy was used to detect changes in the morphological properties of bacteria before and after the PDI treatment.
- MeSH
- Bacteria drug effects radiation effects MeSH
- Photochemical Processes * MeSH
- Photochemotherapy methods MeSH
- Microscopy, Atomic Force MeSH
- Nanoparticles * chemistry MeSH
- Polystyrenes * chemistry MeSH
- Porphyrins administration & dosage chemistry MeSH
- Drug Compounding * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Polystyrenes * MeSH
- Porphyrins MeSH
- tetraphenylporphyrin MeSH Browser
Using coarse-grained dissipative particle dynamics (DPD) with explicit electrostatics, we performed (i) an extensive series of simulations of the electrostatic co-assembly of asymmetric oppositely charged copolymers composed of one (either positively or negatively charged) polyelectrolyte (PE) block A and one water-soluble block B and (ii) studied the solubilization of positively charged porphyrin derivatives (P+) in the interpolyelectrolyte complex (IPEC) cores of co-assembled nanoparticles. We studied the stoichiometric mixtures of 137 A10+B25 and 137 A10-B25 chains with moderately hydrophobic A blocks (DPD interaction parameter aAS=35) and hydrophilic B blocks (aBS=25) with 10 to 120 P+ added (aPS=39). The P+ interactions with other components were set to match literature information on their limited solubility and aggregation behavior. The study shows that the moderately soluble P+ molecules easily solubilize in IPEC cores, where they partly replace PE+ and electrostatically crosslink PE- blocks. As the large P+ rings are apt to aggregate, P+ molecules aggregate in IPEC cores. The aggregation, which starts at very low loadings, is promoted by increasing the number of P+ in the mixture. The positively charged copolymers repelled from the central part of IPEC core partially concentrate at the core-shell interface and partially escape into bulk solvent depending on the amount of P+ in the mixture and on their association number, AS. If AS is lower than the ensemble average ⟨AS⟩n, the copolymer chains released from IPEC preferentially concentrate at the core-shell interface, thus increasing AS, which approaches ⟨AS⟩n. If AS>⟨AS⟩n, they escape into the bulk solvent.
- Keywords
- IPEC, computer simulations, electrostatic co-assembly, porphyrin, solubilization,
- Publication type
- Journal Article MeSH