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 EGFR-specific single chain
fragment antibody (ABX-
EGF scFv). The uptake of ABX-
EGF scFv-modified (LCP-scFv) 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 dual-
ligand LCP NPs may be a valuable targeting system for human
breast cancer diagnosis and
therapy.