Novel porphyrin derivatives: spectroscopic characterization and hemolytic effect on human red blood cells (RBCs)

Porphyrins are an important class of natural and artificial pigments which play an important role in largely different area of both fundamental and technological interest. In particular, porphyrin metal derivatives have been exploited as models for enzymes and artificial blood. Charged porphyrins are able to interact with several relevant biomolecules, i.e., nucleic acids, polypeptides, and proteins. This property together with their ability to localize into tumor cells and to photosensitize the production of singlet oxygen led to the development of several compounds actually in use or under investigation for photodynamic therapy applications (PDT) [1]. Interestingly, quite recently, meso-tetrakis(4-carboxyphenyl) porphyrin (TPPC) and its derivatives have been exploited as a marker for the rapid detection of tumor cells by fluorescence imaging. A common feature of these molecules is their propensity to interact to form dimers, oligomers, or more extended aggregates. To develop efficient systems for biomedical applications or for PDT (in which aggregation should be prevented) or to stabilize monomeric porphyrins in a very water-soluble form, novel systems based on biocompatible delivery systems are highly desirable. In this framework, recently some of us reported on the employment of biocompatible amino-terminated polypropylene or poly(ethylene oxide)s generally termed as Jeffamines, to prevent porphyrin aggregation, allowing to reach millimolar concentration of TPPC in a monomeric form in solution [2]. In biological media, cell membranes seem to be important targets for many antineoplastic photosensitizer agents. Red blood cells have been often used for in vitro PDT studies. Here we report on two different porphyrin derivatives, TPPC-Jeff and ZnTPPC-Jeff. Photodynamic action was then evaluated in vitro using human red blood (HRB) cells under different conditions to obtain information about the effect produced by these porphyrin derivatives. The morphology of erythrocytes has been investigated by optical microscopy after incubation with porphyrin compounds and irradiation having a losing of their normal biconcave profile and an incoming of a spiny configuration with blebs in their surfaces. Further studies are required to optimize potential therapeutic dosing strategies to inform and encourage clinical trial design.