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Targeted delivery of small interfering RNA (siRNA) and chemotherapeutic drugs using nanoparticles (NPs) is a promising strategy to overcome current limitations in treating these metastatic breast cancers. This research develops alendronate conjugated polyethylene glycol functionalized chitosan (ALD\u2010PEG\u2010CHI) NP for the delivery of cell death siRNA (CD\u2010siRNA) and curcumin (CUR) and explores its targeting ability and in vitro cell cytotoxicity. Polyethylene glycol functionalized CHI (mPEG\u2010CHI) NPs serve as control. The size of CD\u2010siRNA loaded NPs is below 100\u00a0nm while CUR loaded NPs is below 200\u00a0nm, with near neutral zeta potential for all NPs. The CUR encapsulation efficiency (EE) is 70% and 88% for targeted and control NPs, respectively, while complete encapsulation of CD\u2010siRNA is achieved in both NP systems. The bone targeting ability of CY5\u2010dsDNA loaded ALD\u2010PEG\u2010CHI NPs using hydroxyapatite discs is fivefold compared to control indicating ALD presentation at the targeting NP surface. Delivery of CD\u2010siRNA loaded NPs and CUR loaded NPs show synergistic and additive growth inhibition effects against MCF\u20107 cells by mPEG\u2010CHI and ALD\u2010PEG\u2010CHI NPs, respectively. Overall, these in vitro results illustrate the potential of the targeted NPs as an effective therapeutic system toward bone metastasized breast cancer.<\/jats:p>","DOI":"10.1002\/mabi.202300268","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:49:35Z","timestamp":1696466975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Targeted Nanoparticles Based on Alendronate Polyethylene Glycol Conjugated Chitosan for the Delivery of siRNA and Curcumin for Bone Metastasized Breast Cancer Applications"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2592-1562","authenticated-orcid":false,"given":"Asim","family":"Mushtaq","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  Cooper Road Brisbane Queensland 4072 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