Photothermal　therapy　(PTT)　is　a　promising　noninvasive　cancer　treatment　with　high　spatial-temporal　selectivity　and　low　systemic　toxicity.　However,　its　efficiency　is　restricted　by　the　poor　photostability,　low　tumor　selectivity　and　inadequate　deep　tumor　penetration　of　current　photothermal　agents.　This　study　synthesized　oleanolic　acid　(OA)-modified　chitosan　(CsO)　using　click　chemistry　and　developed　a　nano-photothermal　agent　(COI)　through　the　self-assembly　of　CsO　and　a　representative　photothermal　agent　indocyanine　green　(ICG).　COI　possessed　a　particle　size　of　approximately　120　nm,　good　physical　stability,　and　pH-responsive　drug　release　properties.　Under　808　nm　laser　irradiation,　COI　exhibited　high　photothermal　conversion　efficiency　and　photostability.　The　cellular　uptake　of　COI　in　B16　and　4T1　cancer　cells　was　several-fold　higher　than　that　of　free　ICG,　while　remaining　comparable　to　ICG　in　normal　3T3　cells.　CsO　inhibited　cancer-associated　fibroblasts　proliferation　and　modulated　the　tumor　microenvironment　by　reducing　α-smooth　muscle　actin　expression,　enhancing　deep　penetration　of　COI　in　three-dimensional　multicellular　tumor　spheres　and　solid　tumors.　The　promising　anti-proliferative　effects　of　COI　in　vitro　and　in　vivo　indicated　notable　synergistic　effects　between　the　chemotherapeutic　effect　of　OA　and　the　photothermal　therapeutic　effect　of　ICG.　These　results　suggest　that　COI　could　serve　as　a　promising　deep　tumor-penetrating　nano-photothermal　agent　for　enhanced　chemo-photothermal　anticancer　therapy.　©　2025　Elsevier　Ltd