Drugs need to be designed to access the designated intracellular organelle compartments in order to maximize anticancer efficacy. This study identified that covalently conjugated, non-covalent polyethylene glycol coated uptake, the intracellular and extracellular trafficking of cancer cells. The types of nano conjugation modulated intracellular dynamics associated with differential impact on anti-cancer efficacy, but also induced differential cytotoxicity on cancer versus normal cells. In conclusion, this study demonstrated the imp appropriate type of nano-conjugation for delivering organelle specific, active chemotherapeutic agents through controlled intracellular trafficking.