Targeted Nanoparticles Based on Alendronate Polyethylene Glycol Conjugated Chitosan for The Delivery of Sirna and Curcumin for Bone Metastasized Breast Cancer Applications.

Bone metastasized breast cancer reduces the quality of life and median survival. Targeted delivery of siRNA and chemotherapeutic drugs using nanoparticles (NPs) is a promising strategy to overcome current limitations in treating these metastatic breast cancers. This research developed alendronate conjugated polyethylene glycol functionalized chitosan (ALD-PEG-CHI) NP for the delivery of cell death siRNA (CD-siRNA) and curcumin (CUR) and explored its targeting ability and in vitro cell cytotoxicity. Polyethylene glycol functionalised CHI (mPEG-CHI) NPs served as control. The size of CD-siRNA loaded NPs was below 100 nm while CUR loaded NPs was below 200 nm, with near neutral zeta potential for all NPs. The CUR encapsulation efficiency was 70 and 88% for targeted and control NPs, respectively, while complete encapsulation of CD-siRNA was achieved in both NP systems. The bone targeting ability of CY5-dsDNA loaded ALD-PEG-CHI NPs using hydroxyapatite discs was 5-fold compared to control indicating ALD presentation at the targeting NP surface. Delivery of CD-siRNA loaded NPs and CUR loaded NPs showed synergistic and additive growth inhibition effects against MCF-7 cells by mPEG-CHI and ALD-PEG-CHI NPs, respectively. Overall, these in vitro results illustrate the potential of the targeted NPs as an effective therapeutic system towards bone metastasized breast cancer. This article is protected by copyright. All rights reserved.