Photodynamic　therapy　(PDT)　utilizing　metal-organic　frameworks　(MOFs)　has　developed　as　a　new　and　efficacious　treatment　for　malignant　tumors　located　on　the　surface　of　the　human　body.　In　order　to　achieve　more　effective　PDT　treatment　outcomes,　the　traditional　method　has　been　to　increase　the　intensity　of　the　laser　irradiation,　but　this　approach　can　easily　lead　to　tissue　burns.　In　this　study,　we　developed　a　new　type　of　nanoparticle,　F68-PKI@PCN224,　aims　to　achieve　effective　PDT　upon　medullary　thyroid　carcinoma　(MTC)　which　is　an　uncommon　form　of　thyroid　cancer　that　originates　in　the　parafollicular　cells　of　the　thyroid　and　the　therapeutic　outlook　for　patients　with　MTC　remains　unsatisfactory.　F68-PKI@PCN224　combines　the　antitumor　features　of　PDT　with　mammalian　target　of　rapamycin　(mTOR)　inhibitor　PKI-587　(PKI).　The　tumor　sensitization,　slow　release,　and　pH　response　features　of　F68-PKI@PCN224　was　demonstrated　by　a　series　of　in　vitro　and　in　vivo　experiments　/　assays.　F68-PKI@PCN224　achieved　the　long-term　activation　and　slow　releasing　of　PKI　and　TCPP　in　MTC　tumor　tissues.　During　the　process　of　generating　PDT　effects,　F68-PKI@PCN224　enhanced　the　tumor＇s　sensitivity　to　PDT,　direct　laser　irradiation　of　MTC　cells　or　subcutaneous　tumor　tissues.　As　a　result,　low-dose　phototherapy　achieves　a　higher　anti-tumor　effect　upon　F68-PKI@PCN224　compared　with　TCPP.　This　study　reveals　the　synergistic　effect　between　tumor　sensitization　by　mTOR　inhibitor　and　PDT　and　initially　unveils　the　mechanism　of　action　of　these　nanoparticles.　©　2024