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Osteosarcoma, as a common malignant neoplasm in children and adolescents, still remains a challenge for conventional therapeutic regimens. In the meantime advent of innovative and revolutionary techniques such as drug delivery systems and smart nano-biomaterials seems promising in tackling these complications. In this study, we designed a smart nano-system consisting of a magnetic inner core and polymeric outer shell with cationic moieties for targeted delivery and enhanced uptake of methotrexate anticancer agent for Saos-2 cell line. The designed nano-formulation was characterized and its drug loading capacity and drug release profile were studied as well that about 60% of methotrexate was released in the first 12 h. The efficacy of the nano-formulation in killing cancer cells was assessed using MTT, cellular uptake, and uptake flow-cytometry. Our in-vitro results confirmed the prepared nano-system …