Usually, conventional chemotherapy of leukemia is not successful, as hematopoietic stem cells change to cancer type. So, it seems designing a new targeting system is necessary to overcome this problem. A nano smart polymer, PMBN conjugated with interleukin 3 as a ligand of the CD123 receptor, which is overexpressed on leukemia stem cells, was used with incorporated paclitaxel or ganoderic acid A, a fungal metabolite, to directly target and treat stem cell cancer. The rate of conjugation was about 75% and rate of loading by PTX and GA-A were about 88% and 77%, respectively. Toxicity and apoptosis analyses show that the nano carrier is more effective than free agents or non-targeted polymers which increase anti-proliferation of cells. The nano targeted polymer has no significant toxicity towards cells that do not express CD123. Generally, the PMBN-IL3-GA conjugate could be an interesting substitution for conventional therapy methods based on chemotherapy agents.