Photosensitizing nanoclays for efficient cell uptake and in vitro photodynamic therapy.

In this study a straightforward strategy to deliver photosensitizing molecules into cancer cells by using Laponite RD® (LAP) nanodisks as carrier is presented. We report the application of LAP functionalized with a highly hydrophobic Silicon phthalocyanine photosensitizer (SiPc) for efficient cell uptake and photodynamic therapy (PDT) of MCF-7 breast cancer cells in vitro. This inorganic-organic hybrid nanomaterial caused a threefold increase in intracellular ROS levels and 99.7% of cancer cell inactivation after light treatment (630 nm; fluency of 108 J/cm²). With its theranostic capabilities (simultaneous fluorescence and singlet oxygen generation), uptake into cancer cells was monitored to control the photo-inactivation. The functionalized nanodisks already proved to be an efficient photo-inactivator of pathogenic Gram-(+) bacteria and were previously reported as LS10. By extending the use of LS10 to PDT of cancer cells, it is an example of a photosensitizer functionalized nanoclay with multipurpose drug characteristics, demonstrating an intriguing potential for future phototherapeutic studies and applications.

Core-sheath nanostructured chitosan-based nonwovens as a potential drug delivery system for periodontitis treatment.

Core-sheath nanofibers were successfully prepared via coaxial electrospinning by using chitosan with well-defined structural characteristics as the shell layer and poly (vinyl alcohol) (PVA) containing tetracycline hydrochloride (TH) as the core layer. The effects of the average degree of deacetylation (DD‾) of chitosan and the post-electrospinning genipin crosslinking on physicochemical and biological properties of resulting nonwovens were evaluated. Defect-free and geometrically uniform nanofibers with diameters predominantly in the range of 100-300 nm were prepared, and transmission electron microscopy (TEM) revealed the core-sheath structures and its preservation after crosslinking. The mechanical properties, as well as the stability of nonwovens in aqueous medium, were greatly improved by genipin-crosslinking, which enabled a sustained release of TH over 14 days. Results also revealed that the release profile of TH in the presence of lysozyme was affected by the composition of the shell layer, as the TH release rate increases with decreasing of DD‾. Further in vitro antimicrobial activity demonstrated that the cross-linked nonwovens containing TH showed strong activity against bacterial strains associated with periodontal disease. Additionally, the nonwovens did not demonstrate cytotoxic toward fibroblast (HDFn) cells, hence showing their potential for applications as a novel drug delivery platform for periodontitis treatment.

Luminescent Mesoporous Silica Nanohybrid Based on Drug Derivative Terbium Complex.

Mesoporous silica nanoparticles prepared by organic template-driven synthesis have been successfully explored as carriers of the drug-derivate green luminescent complex of terbium (III) with the nonsteroidal anti-inflammatory drug ketoprofen. The terbium (III) complex was synthesized by reacting ketoprofen sodium salt with terbium (III) chloride, which was further adsorbed onto the surface of mesoporous nanoparticles with a mean particle size of 47 ± 4 nm and pore size of 11 nm. The incorporation of the complex into mesoporous silica nanoparticles was tracked by the decrease in the surface area and pore size of the nanoparticles, and successfully demonstrated by substantial changes in the adsorption isotherms and thermal and vibrational spectroscopy results. The cytotoxicity assay and confocal microscopy have shown that the novel luminescent nanohybrid presents high cell viability and the characteristic terbium (III) emission can be assessed through two-photon excitation, which paves the way for bioimaging applications in nanomedicine.

Near-infrared photodynamic inactivation of S. pneumoniae and its interaction with RAW 264.7 macrophages.

Pneumonia is the main cause of children mortality worldwide, and its major treatment obstacle stems from the microorganisms increasing development of resistance to several antibiotics. Photodynamic therapy has been presenting, for the last decades, promising results for some subtypes of cancer and infections. In this work we aimed to develop a safe and efficient in vitro protocol for photodynamic inactivation of Streptococcus pneumoniae, one of the most commonly found bacteria in pneumonia cases, using two near-infrared light sources and indocyanine green, a FDA approved dye. Photodynamic inactivation experiments with bacteria alone allowed to determine the best parameters for microbial inactivation. Cytotoxicity assays with RAW 264.7 macrophages evaluated the safety of the PDI. To determine if the photodynamic inactivation had a positive or negative effect on the natural killing action of macrophages, we selected and tested fewer indocyanine green concentrations and 10 J/cm2 on macrophage-S. pneumoniae co-cultures. We concluded that ICG has potential as a photosensitizer for near-infrared photodynamic inactivation of S. pneumoniae, producing minimum negative impact on RAW 264.7 macrophages and having a positive interaction with the immune cell's microbicidal action.

Pneumonia treatment by photodynamic therapy with extracorporeal illumination - an experimental model.

Infectious pneumonia is a major cause of morbidity/mortality, mainly because of the increasing rate of microorganisms resistant to antibiotics. Photodynamic Therapy (PDT) is emerging as a promising approach, as effects are based on oxidative stress, preventing microorganism resistance. In two previous studies, the in vitro inactivation of Streptococcus pneumoniae using indocyanine green (ICG) and infrared light source was a success killing 5 log10 colony-forming units (CFU/mL) with only 10 µmol/L ICG. In this work, a proof-of-principle protocol was designed to treat lung infections by PDT using extracorporeal illumination with a 780 nm laser device and also ICG as photosensitizer. Hairless mice were infected with S. pneumoniae and PDT was performed two days after infection. For control groups, CFU recovery ranged between 103-104/mouse. For PDT group, however, no bacteria were recovered in 80% of the animals. Based on this result, animal survival was evaluated separately over 50 days. No deaths occurred in PDT group, whereas 60% of the control group died. Our results indicate that extracorporeal PDT has the potential for pneumonia treatment, and pulmonary decontamination with PDT may be used as a single therapy or as an antibiotics adjuvant.