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In the last decades the worldwide rise in antibiotic resistance has intensified the development of new antimicrobial agents. Photodynamic antimicrobial chemotherapy (PACT) has been used successfully to inactivate bacteria. We herein report a new zinc phthalocyanine based photosensitizer conjugated with polylysine moiety (ZnPc-PL). This photosensitizer significantly inactivated Porphyromonas gingivalis, the primary pathogenic bacteria responsible for periodontitis. No obvious phototoxicity was found to either mammalian bone marrow stromal cells (BMSC) or human periodontal ligament cells (HPDLC), indicating the high selectivity of ZnPc-PL toward bacteria. Furthermore, we established an experimental periodontitis model on beagle dogs to test the antimicrobial efficacy in vivo. The amount of gingival crevicular fluid (GCF) and the activity of crevicular fluid aspartate aminotransferase (AST) were monitored and were found to reduce significantly in the ZnPc-PL treated group compared to the controls (laser only and no treatment). In addition, PACT with ZnPc-PL caused a reduction in the bacterial burden by 100-fold compared to controls. Taken together, these findings suggest ZnPc-PL is a promising antimicrobial photosensitizer for the treatment of periodontal diseases.