Photothermal　therapy　(PTT)　is　a　type　of　noninvasive,　topical　cancer　treatment　technique　with　photosensitive　reagent　that　thermally　reacts　to　a　local　laser　irradiation　over　malignant　tumor　site.　While　phthalocyanine　(Pc)　variates　are　promising　photosensitizer　candidate　having　an　excellent　optical　property　tuned　to　deep　penetrating　near-infrared　(NIR)-I　window　and　generates　high　yield　of　reactive　oxygen　series,　the　hydrophobic　characteristic　of　Pc　does　not　withstand　to　general　intravenous　administration,　which　greatly　limits　the　dye　to　penetrate　into　tumor　tissue　and　ultimately　lowers　the　treatment　efficacy.　The　noncovalent　conjugation　with　electron-rich　transferrin　(TF)　not　only　increase　the　solubility　of　the　dye,　and　but　also　quench　the　fluorescence　and　incapacitate　strong　photoinduced　electron　transfer　required　for　reactive　oxygen　generation,　which　feeds　back　the　dye　to　transform　into　interconvertible　photothermal　theragnostic　contrast　agent　both　for　photoacoustic　(PA)　imaging　and　PTT.　Moreover,　the　TF　receptor-rich　tumor　cells　are　actively　targetable　and　mediate　high　accumulation　to　the　tumor　site.　The　in　vitro　experiment　demonstrated　the　feasible　PA　absorption　spectra　of　ZnPcN4-TF,　and　extended　aggregation　test　revealed　the　homogeneous　superiority　of　ZnPcN4-TF　compared　to　ZnPcN4　lumps.　Lastly,　the　72-hour　in　vivo　whole-body　photoacoustic　imaging　of　MCF-7　tumor　bearing　mice　was　sequentially　taken　under　two　nominal　wavelengths　(710　nm　as　peak　PA　signal　level,　800　nm　as　noise-equivalent　level).　From　the　result,　the　increased　liver　uptake　verified　the　enhanced　solubility,　and　active　targetability　toward　MCF-7　tumor　cell　appeared　in　54%　PA　signal　level　increase　at　maximum　in　after　8-hour　postinjection.　©　2023　SPIE.