Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death

Alaa A Fadhel,1 Xiling Yue,1 Ebrahim H Ghazvini Zadeh,1 Mykhailo V Bondar,2 Kevin D Belfield3 1Department of Chemistry, University of Central Florida, Orlando, FL, USA; 2Institute of Physics NASU, Kiev, Ukraine; 3Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, University Heights, Newark, NJ, USA Abstract: Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells. Already known for applications in lithography and cationic polymerization, our developed oxygen-independent PDT, whether free or highly monodispersed on SiNPs, generates acid when a one-photon (1P) or two-photon (2P) excitation source is used, thus potentially permitting deep tissue treatment. Our study shows that when conjugated to SiNPs with protruding amine functionalities (SiNP–PAG9), such atypical PDT agents can be effectively delivered into HCT-116 cells and compartmentalize exclusively in lysosomes and endosomes. Loss of cell adhesion and cell swelling are detected when an excitation source is applied, suggesting that SiNP–PAG9, when excited via near-infrared 2P absorption (a subject of future investigation), can be used as a delivery system to selectively induce cell death in oxygen-deprived optically thick tissue. Keywords: oxygen-independent photodynamic therapy, photoacid generator, silica nanoparticles, stimuli-responsive, sulfonium sal

Two-photon anisotropy: Analytical description and molecular modeling for symmetrical and asymmetrical organic dyes

One- and two-photon anisotropy spectra of a series of symmetrical and asymmetrical polymethine (PD) and fluorene molecules were measured experimentally and discussed theoretically within the framework of three-state and four-state models. For all the molecules discussed in this paper, the experimental two-photon anisotropy values, r(2PA), lie in the relatively narrow range from 0.47 to 0.57 and remain almost independent of wavelength over at least two electronic transitions. This is in contrast with their one-photon anisotropy, which shows strong wavelength dependence, typically varying from approximate to 0 to 0.38 over the same transitions. A detailed analysis of the two-photon absorption (2PA) processes allows us to conclude that a three-state model can explain the 2PA anisotropy spectra of most asymmetrical PDs and fluorenes. However, this model is inadequate for all the symmetrical molecules. Experimental values Of r2PA for symmetrical polymethines and fluorenes can be explained by symmetry breaking leading to the deviation of the orientation of the participating transition dipole moments from their 'classical' orientations. (c) 2005 Elsevier B.V. All rights reserved.321325726

Undergraduate physiotherapy students' competencies, attitudes and perceptions after integrated educational pathways in evidence-based practice: a mixed methods study

This mixed methods study aimed to explore perceptions/attitudes, to evaluate knowledge/skills, to investigate clinical behaviours of undergraduate physiotherapy students exposed to a composite education curriculum on evidence-based practice (EBP). Students' knowledge and skills were assessed before and after integrated learning activities, using the Adapted Fresno test, whereas their behaviour in EBP was evaluated by examining their internship documentation. Students' perceptions and attitudes were explored through four focus groups. Sixty-two students agreed to participate in the study. The within group mean differences (A-Fresno test) were 34.2 (95% CI 24.4 to 43.9) in the first year and 35.1 (95% CI 23.2 to 47.1) in the second year; no statistically significant change was observed in the third year. Seventy-six percent of the second year and 88% of the third year students reached the pass score. Internship documentation gave evidence of PICOs and database searches (95-100%), critical appraisal of internal validity (25-75%) but not of external validity (5-15%). The correct application of these items ranged from 30 to 100%. Qualitative analysis of the focus groups indicated students valued EBP, but perceived many barriers, with clinicians being both an obstacle and a model. Key elements for changing students' behaviours seem to be internship environment and possibility of continuous practice and feedback