Projects
1. Design, synthesis, optimization and characterization for improving the two-photon absorption properties of PS for prospective use in PDT, such as encapsulation of a porphyrin PS in acetylated lignin nanoparticles; optimization of the PS Temoporfin® ; design and organic synthesis of new porphyrin-pyrimidine dyads or the expansion of the porphyrin macrocycle using naphthalene and substitution to include heavy elements (thiophene, selenophene, and tellurophene). The nonlinear optical properties of the compound have been evaluated.
2. Optimized PSs require the ability to synthetically easily alter and modify the core macrocycle structure, which has been done through development of a modular synthesis of hydroporphyrins. In depth photophysical studies have shown singlet oxygen production and promise for subsequent cell biological studies.
3. New excitation modes of PS: cyanine have been combined with porphyrins to obtain well defined covalent molecular systems that can use NIR light to generate triplet states and RIS. Investigations have been also included into films.
4. Development and evaluation of radiolabeled theragnostic agents that could be protected and transported to cancerous cells by functionalized cellulose nanocrystals. A series of in vivo tests have confirmed that such hybrid compounds have the potential of generating new drugs and a potential impact on health care. At least, analogous hybrid systems using similar approaches might be able to reach the market and open up new research perspectives.
5. Insertion/encapsulation of PS in hydrogel from biopolymers, such as hyaluronic acids. Different PS like porphyrins, chlorins and bodipy have been synthetized and antimicrobial evaluation have been done.
6. Ideal PSs must possess certain chemical and photophysical characteristics. In order to develop a core structure amenable to chemical functionalization and bioconjugation a [2+2] MacDonald type condensation strategy for oxidation-resistant gem-dimethyl chlorins has been developed and a small library of compounds was prepared and tested.
7. Development of modified lignin nanoparticles and encapsulation of PS in order to investigate their photodynamic effect on planktonic bacteria. Those systems can be loaded with PS and are efficient against Gram-positive strains, very stable vs. time, light and pH. They demonstrated their capabilities to photocatalyze the degradation of highly prescribed antibiotics, allowing an important decrease of the total organic carbon.
8. Study of Redaporfin, a synthetic sulphonamide fluorinated bacteriochlorin, has phenyl-macrocyclic single bonds with hindered rotations that generates a different spatial distribution of the sulphonamide groups in the meta positions. We showed that it is possible to separate the four atropisomers of redaporfin, which were tested regarding their uptake and PDT efficacy. In vitro and in vivo immunomodulatory studies showed that utilization of specific atropisomers constitutes a novel drug delivery principle.
9. Targeted appropriate PS solubility and the ability to achieve modular formulations through appropriate design criteria. Hydrogels were developed as flexible PS delivery agents. The PS have either been bound covalently in the framework of the gel or as inclusion compounds. Synthetic studies with modified temoporfin as PS and cross-linker within the gel gave a highly promising immunostimulatory PDT formulation as shown in vivo.
10. Synthesis and characterization of organometallic-based PS for new PDT applications. The new PS have been tested for the first time on fibroblast-like synoviocytes cells. The in vitro activity was excellent, with IC50 values in the nano-molar range, thus being so far the most active compounds ever tested in such cells. These cells are particularly relevant, as they are linked to rheumatoid arthritis, a disease affecting a large number of the population. The PS appeared to be very promising, a patent application was even envisaged.
