Synergic Influence of Parameters Involved in the Polymeric Nanoparticle Preparation on the Efficacy of Photodynamic Therapy

The challenge was always great for lipophilic photosensitizer use in the photodynamic therapy (PDT) for treatment of internal body diseases. Photosensitizer metabolism in liver, incompatibility of the molecules in the gastric acid, aggregation in the bloodstream, opsonization of molecules and phagocyting process hamper the application of the free lipophilic photosensitizer in disease treatment using PDT. This problem has been partially resolved using the drug delivery system to encapsulate the photosensitizer. Many studies have been reported using polymeric nanoparticles to encapsulate the lipophilic photosensitizer showing excellent results for PDT, but few nanoparticulate formulations are available at the pharmacies. The absence of deep knowledge about the influence of synergic effect of parameters used in the nanoparticle preparation on its properties, the photobleaching process of encapsulated photosensitizer and the molecule aggregation into the nanoparticle can decrease the photodynamic efficacy for the lipophilic photosensitizer. Our research group has studied the influence of many parameters on the nanoparticulate properties of several encapsulated phthalocyanines and porphyrin using factorial design, evaluating the free and encapsulated compound aggregation, efficacy to reduce the viability of cancer cells, the photooxidation of the biomolecules and the influence of photobleaching. This work shows the most important results to be consider in the optimization of the polymeric nanoparticle.

Controlling Molecule Aggregation and Electronic Spatial Coherence in the H-Aggregate and J-Aggregate Regime at Room Temperature

Controlling molecule aggregation in polymer films is one of the key factors in understanding the links between properties and structures in organic semiconductors. Here, we used poly(3-hexylthiophene-2,5-diyl) (P3HT) as the model system. By doping the insulating polar additive poly (ethylene oxide) (PEO) into P3HT film and controlling the processing methods, we achieved the side-to-side H-aggregate and head-to-tail J-aggregate of P3HT molecules with different extents at room temperature. We have demonstrated that the solvent solidification rate plays an important role in the controlling of molecule aggregation, which finally influenced the solid-state phase separation in the film. Furthermore, based on a series of spectroscopy investigations, we quantified the electronic spatial coherence in different aggregations combined with the modified Franck–Condon model. Subsequently, we established the relationship between the processing method, the molecule aggregation, and the electronic spatial coherence.

Theoretical Study on Aggregation of Nuclei-Containing Gas Phase

Haze is a kind of typical heterogeneous nucleation phenomenon in gas phase condensation process. The existence of dust nucleus may induce water molecule aggregation among vapor phase under a certain humidity. In this article, we try to use Density Functional Theory simulation to explore the evolution mechanism of water molecule aggregation influenced by condensation nucleus from the perspective of molecules assembling. We can get the following results: the subcooling degree and physicochemical properties of nucleation center affect the hydrogen bond within the water clusters and the transformation energy barrier of water molecule aggregation tendency. Water vapor begins to heterogeneously condense or forms aggregation humidity in a certain condition based on the center of condensation nuclei. The analysis shows that the effect law of the degree and scale of aggregation or phase transition are influenced by the change of gas phase partial pressure, supersaturated degree along with particle properties. As the energy barrier of nucleation free energy decreases, the formation of water clusters will be easier.

Probing Alzheimer amyloid peptide aggregation using a cell-free fluorescent protein refolding method

Fibrillation of the Alzheimer β-amyloid peptide (Aβ) and (or) formation of toxic oligomers are key pathological events in Alzheimer’s disease. Several strategies have been introduced to identify small molecule aggregation inhibitors, and based on these methods, a number of aggregation inhibitors have been identified. However, most of these methods use chemically synthesized Aβ42 peptides, which are difficult to maintain in a monomeric state at neutral pH where anti-aggregation screening is usually carried out. We have developed a cell-free Aβ42 aggregation assay based on fluorescence protein refolding. This assay utilizes nanomolar concentrations of protein. We genetically fused Aβ42 to the N-terminus of vYFP, a variant of of GFP, and expressed and purified the folded fusion protein. The refolding efficiency of Aβ42–vYFP fusion was inversely correlated with the solubility of Aβ42. Using fluorescence to monitor refolding of Aβ42–vYFP, we confirmed that Zn2+ binds to Aβ42 and increases its aggregation. The IC50 value estimated for Zn binding is 3.03 ± 0.65 µmol/L. We also show that this technique is capable of monitoring the aggregation of chemically synthesized Aβ42.