Sonodynamic　therapy　(SDT)　is　expected　to　be　a　promising　novel　therapeutic　strategy　for　non-invasive　cancer　treatment.　Rose　bengal　(RB),　which　serves　as　a　typical　photosensitizer,　can　also　be　activated　by　ultrasound　and　has　high　potential　to　be　a　sonosensitizer　for　SDT.　However,　the　fast　elimination　rate　and　poor　tumor　accumulation　of　RB　greatly　limit　its　in　vivo　applications.　The　aim　of　this　work　is　to　synthesize　a　rose　bengal　derivative　(rose　bengal　ω-carboxyheptyl　ester,　RBD),　prepare　chitosan　(CS)/RBD　complex　nanoparticles　(RBDCNs),　and　investigate　the　cellular　uptake　and　tumor　accumulation　of　RBDCNs　in　cancer　cell　lines　and　a　transplanted　colon　cancer　mouse　model.　CS　and　RBD　could　form　complex　nanoparticles　with　a　particle　size　of　150-200　nm　and　positive　surface　charges　(＞+40　mV)　at　a　mass　ratio　1.　The　addition　of　CS　conferred　a　remarkable　decrease　in　the　fluorescent　intensity　of　RBD,　suggesting　the　inclusion　of　dye　within　the　complex　nanoparticles.　RBDCNs　showed　good　stability　in　the　medium　containing　salt　ions　with　dye　leakage　of　less　than　20%,　while　the　high　concentration　of　serum　could　affect　the　interaction　between　CS　and　RBD,　resulting　in　about　75%　dye　leakage　under　a　10%　FBS　condition.　RBDCNs　could　achieve　more　efficient　cellular　uptake　in　HT29　and　HepG2　cells　than　RB,　RBD,　or　CS/RB　complex　nanoparticles　(RBCNs).　The　high　accumulation　of　RBDCNs　in　tumors　was　also　observed　when　RBDCNs　were　intravenously　injected　into　CT-26　colon　cancer　transplanted　Balb/c　mice.　These　results　suggested　that　RBDCNs　could　be　efficient　and　promising　tumor　targeting　delivery　systems.　This　journal　is　©　The　Royal　Society　of　Chemistry　2015.