Metastatic　relapse,　development　of　drug　resistance　in　cancer　cells　and　adverse　side　effects　of　chemotherapeutic　agents　are　the　major　obstacles　for　effective　chemotherapy　against　triple-negative　breast　cancer.　To　address　these　problems,　miR-34a,　a　potent　endogenous　tumor　suppressive　molecule　in　breast　cancer,　was　co-encapsulated　with　doxorubicin　(DOX)　into　hyaluronic　acid　(HA)-chitosan　(CS)　nanoparticles　(NPs)　and　simultaneously　delivered　into　breast　cancer　cells　for　improved　therapeutic　effects　of　drug.　DOX-miR-34a　co-loaded　HA-CS　NPs　were　successfully　prepared　through　ionotropic　gelation　method　in　water.　In　vitro　and　in　vivo　experiments　showed　that　miR-34a　and　DOX　can　be　efficiently　encapsulated　into　HA-CS　NPs　and　delivered　into　tumor　cells　or　tumor　tissues　and　enhance　anti-tumor　effects　of　DOX　by　suppressing　the　expression　of　non-pump　resistance　and　anti-apoptosis　proto-oncogene　BcI-2.　In　addition,　intracellular　restoration　of　miR-34a　inhibited　breast　cancer　cell　migration　via　targeting　Notch-I　signaling.　The　obtained　data　suggest　that　co-delivery　of　DOX　and　miR-34a　could　achieve　synergistic　effects　on　tumor　suppression　and　nanosystem-based　co-delivery　of　tumor　suppressive　miRNAs　and　chemotherapeutic　agents　may　be　a　promising　combined　therapeutic　strategy　for　enhanced　anti-tumor　therapy.　(C)　2014　Elsevier　Ltd.　All　rights　reserved.