Conjugation of phthalocyanine photosensitizer with poly(amidoamine) dendrimer: improved solubility, disaggregation and photoactivity against HepG2 cells.

Objective: To improve solubility and to reduce aggregation, ZnPcC4 was conjugated to a third-generation poly-amidoamine dendrimer with amino end group ( G3-PAMAM-NH2), which acts as a novel photodynamic therapy (PDT) drug carrier system. Methods: The phthalocyanines were synthesized by construction reaction. The nano drug was obtained from the conjugation of ZnPcC4 to G3-PAMAM-NH2, using EDC and NHS as coupling agents. The ZnPcC4@G3-PAMAM-NH2 conjugation was characterized by UV-Vis and MS. The O-1(2) quantum yield of ZnPcC4@G3-PAMAM-NH2 in water was measured by the chemiluminescence method. The in vitro PDT responses of the studied photosensitizers were studied in hepatocellular carcinoma cell line HepG2 by MIT assay. Results: At ZnPcC4/G3-PAMAM-NH(2)raw ratio of 100/1, the ZnPcC4 conjugate had improved solubility and reduced aggregation tendency in aqueous solution. At this optimum molar ratio, ZnPcC4-G3-PAMAM-NH2 inhibited HepG2 cells, with a half-maximal inhibitory concentration of 1.67 mu g/mL upon infrared light exposure. The controls, including dark conditions, or media as well as G3-PAMAM-NH2 exposure, exhibited no inhibitory response. Conclusion: The conjugation of phthalocyanine photosensitizer ZnPcC4 to poly-amidoamine dendrimer G3-PAMAM-NH2 improved the PDT outcomes, in which the optimized binding ratio of ZnPcC4 to G3-PAMAM-NH2 was 6:1.