Journal
NANOSCALE
Volume 10, Issue 9, Pages 4258-4266Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr08644j
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Funding
- Australian Research Centre (ARC) Future Fellowship [FT120100813]
- ARC DP grant [DP170104643]
- Chinese Scholarship Council (CSC)
- NIH grants [CA198999, DK100664]
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The conjugation of ligands to nanoparticle platforms for the target delivery of therapeutic agents to the tumor tissue is one of the promising anti-cancer strategies. However, conventional nanoparticle platforms are not so effective in terms of the selectivity and transfection efficiency. In this study, we designed and developed a dual-target drug/gene delivery system based on lipid-coated calcium phosphate (LCP) nanoparticles (NPs) for significantly enhanced siRNA cellular uptake and transfection efficiency. LCP NPs loaded with therapeutic siRNA were conjugated with a controlled number of folic acid and/or EGFRspecific single chain fragment antibody (ABX-EGF scFv). The uptake of ABX-EGF scFv-modified (LCPscFv) and folic acid-modified LCP NPs (LCP-FA) by human breast tumor cells (MDA-MB-468) was significantly higher with an optimal ligand density on each NP surface (LCP-125scFv and LCP-100FA). Co-conjugation with sub-optimal dual ligands (50 FA and 75 ABX-EGF scFv) per LCP NP (LCP-50FA-75scFv) further enhanced the cellular uptake. More significantly, much more NPs were delivered to the MDA-MB-468 tumor tissue in the nude mouse model when LCP-50FA-75scFv NPs were used. Therefore, the new dualligand LCP NPs may be a valuable targeting system for human breast cancer diagnosis and therapy.
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