The　major　challenges　in　photodynamic　therapy　(PDT)　are　the　neutralization　of　cytotoxic　reactive　oxygen　species　(ROS)　by　the　excessive　antioxidant　glutathione　(GSH)　in　tumor　cells,　high　self-aggregation　of　most　photosensitizers　(PSs),　and　long　time　to　protect　from　light　after　treatment.　Thus,　to　develop　the　molecular　PSs　for　the　improved　and　safe　PDT　in　clinic,　a　novel　and　versatile　PS　(Mal-Pc)　has　been　designed　by　di-substituting　maleimides　to　the　axial　positions　of　silicon　(Ⅳ)　phthalocyanine.　Owning　to　the　conjugation　of　maleimides,　Mal-Pc　can　not　only　entry　tumor　cells　more　easily　and　faster,　but　also　can　react　with　the　intracellular　overexpressed　GSH　after　entry.　In　addition,　upon　electrophilic　reaction　with　GSH,　the　inhibition　of　self-aggregation　of　Mal-Pc　has　been　demonstrated　by　the　restoration　of　the　fluorescence　emission　in　aqueous　media.　As　a　result,　the　intracellular　ROS　levels　and　photocytotoxicity　of　Mal-Pc　are　dramatically　enhanced.　Finally,　the　high　hydrophilicity　of　the　product　GS-conjugates　facilitates　Mal-Pc　eliminate　from　the　normal　cells　more　rapidly.　Overall,　this　work　revealed　the　high　potential　of　the　versatile　molecular　Mal-Pc　for　highly　efficient　and　safe　PDT　in　clinical　translation.　©　2022　Elsevier　Masson　SAS