The interaction of chlorin photosensitizers for photodynamic therapy with blood transport proteins

Abstract

Photodynamic therapy (PDT) is still considered to be a promising antitumor modality whose potential is not fully disclosed. This unique combination of visible light, molecular oxygen and a light-sensitive molecule, i.e. a photosensitizer (PS), leads to a generation of reactive oxygen species inducing direct tumor cell death, damage to tumor microvasculature and induction of a local inflammatory reaction. A much higher selectivity of tumor targeting during PDT can be achieved by the PS binding to appropriate delivery vehicles with pronounced affinity to tumor tissue. Blood lipoproteins are often considered to be such agents enhancing PS tumor accumulation. Here, we focus on the interaction between a series of charged chlorin PSs synthesized on a chlorophyll a platform with blood transport proteins. The ability of PS molecules to form molecular complexes with potential carries – biocompatible polymers or surfactants is also considered and briefly discussed. Our experimental studies do indicate that a charge sign, number and relative position of charged groups in the macrocyclic molecule strongly influence the PS-protein interaction. The monocationic chlorin PS with a pronounced hydrophobic surface is found to be delivered by lipoproteins, while trianionic chlorin e6 is preferentially associated with serum albumin. The addition of biocompatible micellar or polymeric carriers widely used to improve biocompatibility of many drugs remains an elution profile almost unchanged despite strong PS-carrier binding. It is important that both di- and tricationic chlorins are not associated with any transport proteins and the mechanism of their accumulation in tumors must be different from other PSs. Taking into account that lipoproteins are highly important carriers for PS molecules in antitumor photodynamic therapy, we can make an important conclusion that chlorins bearing one cationic group at a certain position of a macrocycle are more efficient photosensitizing agents compared to anionic or polycationic macrocycles.