Francis Baros

Inorganic Nanoparticles for Photodynamic Therapy.

Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters.

Synthesis and behaviour study of amphiphilic polyvinylimidazolium salts in aqueous media: Effects of the microdomains on a bimolecular reaction involving hydrophobic reactants

Abstract Homopolymers of 3-alkyl-1-vinylimidazolium bromides series have been prepared by free radical polymerization in aqueous solution or in benzene. The tendency of aggregation of these water soluble polymers was studied by viscosity measurements and fluorescence probes which have revealed the formation of hydrophobic microdomains. These polymers were tested in water media as a macromolecular matrix for the introduction of a microenvironment able to induce an acceleration effect for a bimolecular reaction involving two hydrophobic reactants. The reaction rates of 5(6)-decylbenzimidazole on the hydrolysis of 4′-nitrophenyl-5-alkoxypicolinates in the presence of the poly(3-hexadecyl-l-vinylimidazolium bromide) or its low molecular weight analogue at pH = 7.09, T = 30° C were estimated and compared.

Kinetics of partly diffusion-controlled reactions. XVI: The use of liquid state physics for fluorescence quenching models

Abstract Theories of partly diffusion-controlled reaction kinetics are re-investigated, taking into account the existence of a non-uniform radial distribution function. This allows us to partially explain some discrepancies occurring when molecular emission spectroscopy experiments are carried out using continuous or pulsed excitation.

Stability of folic acid under several parameters

Folic acid is a small molecule, also known as vitamin B9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O2etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies.

Lateral diffusion in synthetic membranes: models and experiments on protein influence

Diffusion-influenced theories of the Smoluchowsky type are applied to the case of synthetic membranes in which a fluorescent probe (pyrene) is included. These models make the assumption of a pseudo-two-dimensional medium with some refinements such as the curvature of space or the thickness of the membrane. After having shown that it is possible to measure a diffusion coefficient inside the membranes with photophysical methods and to characterize the effects of the temperature and of the length of the carbon chains on the lateral diffusion, some proteins are added to the membranes in order to observe their influence on the lateral molecular transport.

Poly(N-alkylacrylamide-co-vinylpyridinium): synthesis and aqueous solution properties

Copolymers of 4-vinylpyridine and N-alkylacrylamides (alkyl chain bearing 6, 10 and 12 carbon atoms) were prepared by bulk free radical copolymerization using 2,2′-azobisisobutyronitrile and 2,2′-azobis(2,4-dimethylvaleronitrile) as initiators. Poly(N-alkylacrylamide-co-4-vinylpyridine)s were then converted into cationic copolymers by quaternization of the pyridine rings with methylbromide. Their amphiphilic properties in dilute aqueous media were studied by viscosimetry, fluorescence and tensiometry. In selected solvents (water + methanol), the association phenomenon was investigated as a function of the solvent composition and the chemical structure of the copolymers.

A Photosensitizer Lanthanide Nanoparticle Formulation that Induces Singlet Oxygen With Direct Light Excitation, But Not By Photon or X-ray Energy Transfer

We report the design and synthesis of europium‐doped gadolinium oxysulfide nanoscintillators Gd2O2S:Eu3+ conjugated with two different photosensitizers (PSs): a zinc chlorin (ZnTPC) and a zinc phtalocyanine (ZnPc) by covalent bonding through a layer of N‐(3‐trimethoxysilylpropyl)diethylenetriamine (TPDA). These conjugates were designed to be activated under X‐ray excitation to allow a photodynamic effect, although this desired outcome was not achieved in this study. The monodispersed nanoparticles of ∼70 nm diameter were pegylated to be stabilized in aqueous suspension. It was shown that the PSs conserved their photophysical properties once conjugated to the nanoscintillator and efficient singlet oxygen was obtained upon photo‐irradiation. However, no energy transfer was observed from the nanoscintillator to the photosensitizer neither under photo‐ nor X‐ray irradiation.

Chapter 10:Production of Singlet Oxygen by Nanoparticle-Bound Photosensitizers

New improvements in the field of targeted PDT concern the use of nanoparticles that can serve as carriers for anticancer agent delivery. Nanoparticles do indeed offer many advantages such as good colloidal stability, effective protection of encapsulated drugs against enzymes and hydrolysis, surface tailor ability and multipurpose, and easy, synthesis. More importantly, thanks to their size, nanoparticles are a means to allow selective accumulation of the PS in cancer cells due to the enhanced permeability and retention effect of tumor tissues. In this chapter, we will focus on the production of singlet oxygen (1O2*) after excitation of PS coupled or encapsulated into nanoparticles possessing a three-dimensional rigid matrix. We define three types of nano-objects: nanoparticles in which the ΦΔ of photosensitizers increases compared to free photosensitizers, nanoparticles in which the ΦΔ of the encapsulated PS decreases compared to ΦΔ of the free photosensitizer and systems in which ΦΔ of the encapsulated or free PS are similar.

Kinetics of partly diffusion-controlled reactions. Part 23.—The case of ionic reactions

Diffusion-controlled reactions have been investigated for many years, and have been modelled for the case where Brownian particles move in a medium of hard spheres. We here present models based upon liquid physics concepts and known interaction potentials for cases where the transport phenomenon is due to a random walk hampered by the electrostatic potential and screen effect.Our model assumes the diffusing particles to be spheres, of identical radius and with a central charge. A ‘continuum’ model is developed which combines the radial configurational function of hard spheres and the Debye–Huckel interaction potential. The solution of a classical integro-differential system then allows us to compute the apparent rate constant of the reaction.This model is applied to the interpretation of the fluorescence quenching of fluorescein ions by iodide ions, a well known system for which several unsatisfactory models (especially static or non-diffusional quenching) have been proposed. The use of the present model, where coupling between diffusion and reactivity is taken into account, makes it possible to find a satisfactory agreement with experiment. However, theoretical refinements are yet required for a better understanding of the phenomenon occurring at low relative permittivity.

Three-Dimensional Fluorescence Microscopy of Endothelial Cells Labeled with Coumarins

Fluorescent coumarins were synthesized with the objective of introducing a glucosamine part in the chemical structure, with either hydroxyl or acetyl functions. The photophysical behavior was studied in organic solvents with different polarity and viscosity. The location of the fluorescent coumarins in endothelial cells was studied using fluorescence microscopy imaging, especially with a 3-D CELLscan instrument.