Affiliation:
1. School of Chemistry and Molecular Biosciences The University of Queensland Cooper Road Brisbane Queensland 4072 Australia
2. Australian Institute for Bioengineering and Nanotechnology The University of Queensland Corner of College and Cooper Road Brisbane Queensland 4072 Australia
Abstract
AbstractBone metastasized breast cancer reduces the quality of life and median survival. 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‐PEG‐CHI) NP for the delivery of cell death siRNA (CD‐siRNA) and curcumin (CUR) and explores its targeting ability and in vitro cell cytotoxicity. Polyethylene glycol functionalized CHI (mPEG‐CHI) NPs serve as control. The size of CD‐siRNA loaded NPs is below 100 nm while CUR loaded NPs is below 200 nm, 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‐siRNA is achieved in both NP systems. The bone targeting ability of CY5‐dsDNA loaded ALD‐PEG‐CHI NPs using hydroxyapatite discs is fivefold compared to control indicating ALD presentation at the targeting NP surface. Delivery of CD‐siRNA loaded NPs and CUR loaded NPs show 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 toward bone metastasized breast cancer.
Funder
National Health and Medical Research Council
Subject
Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering,Biotechnology