Su Chen (2016)

Synthesis and photobiological evaluations of porphyrine dimers for targeted two-photon photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a new potential treatment against retinoblastoma, which doesn’t induce mutations. The porphyrin derivatives used as Ps in PDT are widely studied since the birth of the first synthesis Ps (HpD). An important limitation of PDT comes from low penetration of light (λ<700 nm) used for excitation of the Ps. In order to provide enough energy to enable production of singlet oxygen in the phototherapeutic window between 700-1300, the absorption of two relatively low-energy photons simultaneously has been proposed. Ps excited by simultaneous absorption of two photons leads to the concept of two-photon PDT (TPE-PDT). This process has very low probability; its application in the PDT needs develop new Ps with intensive cross section. Another limitation is the low selectivity and specificity of current Ps for tumor cells. Active targeting to appropriate receptors expressed at the tumor cells give a possible solution. It has been reported that the lectin-like receptors recognizing certain sugars are overexpressed in malignant cells. We will present the synthesis and in vitro photocytotoxical results of asymmetric porphyrin dimers P-Y-P’, inspired by previous studies of our laboratory, introducing three para-phenoxy-diethylene glycol mannose chains at the meso positions of porphyrin core which optimized for two-photon absorption and targeted to membrane lectins. To circumvent the solubility problem of porphyrin dimers in aqueous medium and improve internalization of Ps into tumor cells, we analyzed the interfacial behavior of the porphyrin dimers in the air-buffer interface, studied the incorporation of porphyrin dimers in liposomes using the technique of fluorescence, and evaluated the interaction between porphyrin dimers and Concanavalin A (Canavalia ensiformis lectin derived from that specifically recognizes the alpha-D-mannose). (Defended on February 15, 2016)