Non-invasive　monitoring　of　the　in　situ　drug　release　in　a　real-time　manner　is　crucial　for　the　clinical　cancer　treatment.　In　this　work,　a　polymeric　prodrug,　P(HPMA-co-(CPT-SS-CyN)),　composed　of　N-(2-hydroxypropyl)　methacrylamide　(HPMA)　and　a　functional　monomer　(a　near-infrared　fluorescent　cyanine-amine　dye　(CyN)　and　camptothecin　(CPT)　linked　by　disulfide　bond)　was　reported　for　the　non-invasive　and　real-time　reporting　drug　release.　The　cleavage　of　the　disulfide　bond　intracellularly　could　lead　to　the　release　of　free　CPT　as　well　as　the　blue　shift　of　the　dye　(CyN　conjugated　polymer),　enabling　facile　monitoring　of　the　drug　release.　Moreover,　the　percentage　of　the　released　drug　showed　a　linear　correlation　with　the　normalized　increase　in　the　fluorescence　intensity,　which　can　be　further　used　for　the　quantification　of　the　local　drug　concentration.　In　vitro　cell　study　showed　that　the　fluorescence　intensity　gradually　increased　with　the　prolongation　of　incubation　time,　and　P(HPMA-co-(CPT-SS-CyN))　exhibited　the　same　inhibition　efficiency　of　tumor　cell　proliferation　as　CPT.　This　work　may　guide　researchers　for　the　precise　design　and　development　of　various　pharmaceutical　formulations.　©　2020　Elsevier　B.V.