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Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles (∼62.5 nm in diameter) with high drug loading efficiency (∼16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.