RNAi based gene silencing is a novel and environmental sustainable technique to control pests in crops and plants. Cationic polymers act as an important transfection agent thus improving the stability and efficiency of the process.

Osteosarcoma (OS) is a malignant tumor, fatal for pediatric patients who do not respond to chemotherapy, alternative therapies and drugs can provide better outcomes. Zoledronic acid (Zol) belonging to the class of bisphosphonates (BPs) has a direct antitumor ability to prevent Ras GTPases modification and stimulate apoptosis. Despite advances in maintaining balance in skeletal events and direct anticancer properties, Zol causes cytotoxicity to normal healthy pre‐osteoblast cells, hampering mineralization and differentiation. The study reports the preparation and evaluation of a nanoformulation that can diminish the existing drawbacks of native Zol. The cytotoxic effect is evaluated on bone cancer cells and healthy bone cells with three different cell lines namely, K7M2 (mouse OS cell line), SaOS2 (human OS cell line), and MC3T3E1 (healthy cell counterpart). It is observed that Zol nanoformulation is uptaken more (95%) in K7M2 whereas in MC3T3E1, the percent population internalizing nanoparticles (NPs) is 45%. Zol has a sustained release of 15% after 96 h from the NP which leads to a rescuing effect on the normal pre‐osteoblast cells. In conclusion, it can be stated that Zol nanoformulation can be used as a good platform for a sustained release system with minimum side effects to normal bone cells.