Based on the observation that the application of small amounts of exogenous acid sphingomyelinase to generate endogenous ceramide, or provision of exogenous long-chain natural C16-ceramide resulted in rapid translocation of vacuolar daunorubicin into the nucleus in multi-drug resistant (MDR) cells, the present invention relates to a nano-liposomal preparation that includes C16-ceramide. Exposure of MDR cells to the C16:0 ceramide-based nanoliposomes provide a mechanism to reverse MDR in chemoresistant cells and tumors, by inducing rapid translocation of chemotherapeutic agent from cytoplasmic vesicles to the nucleus.