Advanced　prostate　cancer　is　regarded　as　a　fatal　disease,　characterized　by　limited　treatment　options,　poor　prognosis　and　considerable　tumor　metastasis　closely　related　to　angiogenesis.　Photodynamic　therapy　emerges　as　a　promising　and　safe　therapeutic　modality　for　advanced　prostate　cancer　with　high　metastasis　and　high　fatality　rate　due　to　its　focal　damage　to　tumor　cells,　as　well　as　its　anti-angiogenesis　and　antitumor　immunity　capabilities.　Herein,　a　tumor-targeting　vascular　disrupting　agent　ASA-404　was　introduced　to　conjugate　with　a　photosensitizer　ZnPc　for　targeted　prostate　cancer　treatment　and　enhanced　vascular-disrupting　efficiency.　Notably,　this　novel　organic　small-molecule　photosensitizer　Pc-ASA　possess　a　well-defined　chemical　structure　and　purity,　as　well　as　good　photophysical　and　photochemical　properties,　which　are　of　benefit　for　clinical　approval　and　application.　Pc-ASA　prefers　to　accumulate　in　both　prostate　cancer　cells　and　vascular　endothelial　cells.　Moreover,　the　conjugation　of　ASA-404　boosts　the　photodynamic　anticancer　effect　of　Pc-ASA　towards　both　prostate　cancer　cells　and　vascular　endothelial　cells.　Ultimately,　PC-ASA　can　successfully　inhibit　the　migration　and　metastasis　of　prostate　cancer　cells,　offering　significant　advantages　in　advanced　prostate　cancer　management.　Our　study　might　open　a　window　in　the　development　of　the　tumor　and　vascular　dual-targeted　small-molecule　photosensitizers,　with　the　potential　to　achieve　safe　and　efficient　treatment　of　metastatic　advanced　prostate　cancer　through　dual　mode　of　antitumor　and　anti-vascular　action.　©　2024　Elsevier　Ltd