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Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecular charge transfer efficiency. <jats:bold>I<\/jats:bold><jats:sub><jats:bold>2<\/jats:bold><\/jats:sub><jats:bold>-IR783-Mpip<\/jats:bold> exhibited good photodynamic efficiency towards liver hepatocellular carcinoma cells under physiological and slightly acidic conditions while normal human embryonic kidney cells remained alive under the same conditions. Detection of intracellular reactive oxygen species (ROS) in cells treated with <jats:bold>I<\/jats:bold><jats:sub><jats:bold>2<\/jats:bold><\/jats:sub><jats:bold>-IR783-Mpip<\/jats:bold> after NIR light exposure confirmed PDT efficiency of the probe in acidic environment. Moreover, <jats:bold>I<\/jats:bold><jats:sub><jats:bold>2<\/jats:bold><\/jats:sub><jats:bold>-IR783-Mpip<\/jats:bold> also demonstrated efficient phototoxicity under deep-seated tumour cell system. 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