Céline Frochot

Silica-based nanoparticles for photodynamic therapy applications

Silica-based nanoparticles for applications in photodynamic therapy (PDT) have emerged as a promising field for the treatment of cancer. In this review, based on the pathway the photosensitizer is entrapped inside the silica matrix, the different methods for the synthesis of silica-based nanoparticles are described from the pioneering works to the latest achievements which concern multifunctional nanoplatforms, up-converting nanoparticles, two-photon PDT, vectorization and in vivo applications.

Influence of the gelator structure and solvent on the organisation and chirality of self-assembling fibrillar networks

Chromophoric probes of naphthalimide moieties enable evaluation of their assembling behaviour photophysically through fluorescence spectroscopy and microscopy, and circular dichroism. These experiments highlight the influence of the nature of the chemical substitution of the organogelator. Very interesting results were also obtained by performing CD experiments showing that the nature of the solvent should modify the chirality of self-assembled aggregates. Highly oriented network structures were observed in the gel state and disappeared in isotropic solution. Microfibrous self-aggregation of organogels is in situ observed via fluorescence and SHG imaging and confirmed by transmission electron microscopic analysis of the dried sample.

Banana-shaped biphotonic quadrupolar chromophores: from fluorophores to biphotonic photosensitizers

This study aims at designing dual-role biphotonic chromophores that could be used for photodynamic therapy (PDT) while maintaining some fluorescence in order to locate them, thus allowing selective irradiation of cancer cells when combined with targeting. Quadrupolar two-photon absorbing fluorophores were synthesized from the symmetrical functionalization of a fluorene core bearing elongated conjugated rods made from arylene–vinylene or arylene–ethynylene building blocks in order to test modifications which could increase singlet oxygen production ability while retaining some fluorescence and high two-photon absorption (TPA) cross-sections in the biological spectral range of interest. All chromophores show a polar emissive excited state whose dipole moment is highly dependent on the nature of the conjugated linker. Interestingly, the largest TPA responses in the NIR region as well as singlet oxygen quantum yield are correlated with the smallest dipole moment of the emissive excited-state. The molecular optimization study led to a multifunctional biphotonic chromophore combining high TPA cross-sections in the whole spectral range of interest (700–900 nm), reasonable singlet oxygen production efficiency, significant remaining fluorescence, and alcohol end-groups for further covalent grafting. This compound offers thus interesting potentialities for highly selective spatially-resolved two-photon PDT by incorporation in nanostructures.

Mechanical and Biological characterization of A Porous Poly‐L‐Lactic Acid‐Co‐ϵ‐Caprolactone scaffold for Tissue Engineering

This article presents a method for making highly porous biodegradable scaffold that may ultimately be used for tissue engineering. Poly(L‐lactic‐co‐ϵ‐caprolactone) acid (70∶30) (PLCL) scaffold was produced using the solvent casting/leaching out method, which entails dissolving the polymer and adding a porogen that is then leached out by immersing the scaffold in distillated water. Tensile tests were performed for three types of scaffolds, namely pre‐wetted, dried, and UV‐irradiated scaffolds and their mechanical properties were measured. The pre‐wetted PLCL scaffold possessed a modulus of elasticity 0.92±0.09 MPa, a tensile strength of 0.12±0.03 MPa and an ultimate strain of 23±5.3%. No significant differences in the modulus elasticity, tensile strength, nor ultimate strain were found between the pre‐wetted, dried, and UV irradiated scaffolds. The PLCL scaffold was seeded by human fibroblasts in order to evaluate its biocompatibility by Alamar blue® assays. After 10 days of culture, the scaffolds showed good biocompatibility and allowed cell proliferation. However, the fibroblasts stayed essentially at the surface. This study shows the possibility to use the PLCL scaffold in dynamic mechanical conditions for tissue engineering

Nanoparticles for Photodynamic Therapy Applications

Photodynamic therapy has emerged as an alternative to chemo- and radiotherapy for the treatment of certain types of cancer. Nanoparticles have been used to improve the delivery and the efficiency of the photosensitizer as they allow its encapsulation without loss of activity. Using targeting strategies, they can also allow the selective accumulation of the photosensitizer in the cancer tissues. In this review, based on the chemical nature of the nanoparticles, the different methods for their syntheses are described from the pioneering works to the latest achievements. Indeed the nanosystems can be conjugated to a biomolecule or an antibody to target receptors over-expressed in cancer cells and/or angiogenic vascular endothelial cells. Numerous in vivo and in vitro applications have been described. Multifunctional nanoplatforms combining several applications within the same nano-object emerge as potential important theranostic tools.

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.

Inactivation of Malaria Parasites in Blood: PDT vs Inhibition of Hemozoin Formation

Malaria causes hundreds of thousands of human deaths every year, and the World Health Assembly has made it a priority. To help eliminate this disease, there is a pressing need for the development and implementation of new strategies to improve the prevention and treatment, due in part to antimalarial drug resistances. This chapter focuses on two strategies to inactivate the malaria parasite in blood, which are photodynamic therapy (PDT) and inhibition of hemozoin formation. The PDT strategy permits either a control of the proliferation of mosquito larvae to develop some photolarvicides for the prevention or a photoinactivation of the malaria parasite in red blood cells (RBCs) to minimize infection transmission by transfusion. The inhibition of hemozoin formation strategy is used for the development of new antimalarial drug by understanding its formation mechanism.

Confocal Microscopy Observation of CHO Cells Cultivated in Presence of Fluorescent – Labelled Rapeseed Peptides

Plant peptides of a rapeseed peptone were labelled with a coumarin fluorescent probe. The free-probe does not incorporate cell cytoplasm and is not cytotoxic at a concentration below 10 μM. Observations by Confocal Microscopy of CHO cells incubated in presence of labelled peptides indicate no fixation of the peptides on cell membrane receptors, but their incorporation inside cell cytoplasm. This integration seems to be time-dependant while the fluorescence intensity reaches saturation after more than 12 hours of incubation.