Conjugates of folic acids with zinc aminophthalocyanine for cancer cell targeting and photodynamic therapy by one-photon and two-photon excitations.

Abstract

To improve the photodynamic detection and therapy of cancers (PDT), folic acid (FA) was conjugated with zinc tetraaminophthalocyanine (ZnaPc) to form ZnaPc-FA. The uptake efficiency of ZnaPc-FA to a FR-positive (folate receptor overexpressed) KB cell line (human nasopharyngeal epidermal carcinoma) was much higher than that of ZnaPc demonstrating an enhanced binding ability of ZnaPc-FA to KB cells. When KB cells were pretreated with free FA followed by incubation of ZnaPc-FA, the high uptake rate of ZnaPc-FA disappeared which demonstrated the special binding function of the FA terminal of ZnaPc-FA on KB cells. The confocal fluorescence images further showed that the affinity of ZnaPc-FA to FR-negative A549 cells (human lung epithelial carcinoma cancer cells) was very low, confirming that ZnaPc-FA can only target FR-positive cancers. The two-photon absorption cross-section of ZnaPc-FA was also higher than that of sulfonated aluminum phthalocyanine (AlPcS), an approved PS for clinical applications. With a 780 nm femto-second (fs) laser, the fluorescence image of ZnaPc-FA in KB cells under two-photon excitation (TPE) can be clearly seen, and the two-photon induced singlet oxygen in ZnaPc-FA solution was found to be proportional to the irradiation dose of the fs laser. The PDT damaging effect of ZnaPc-FA on KB cells was much effective relative to AlPcS under common one-photon excitation, and the killing efficacy of ZnaPc-FA under TPE was 10-fold higher than that of AlPcS. These results suggest that ZnaPc-FA is a promising candidate for PDT improvements and particularly for TPE PDT.