Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands

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 st...

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Bibliographic Details
Published inNanoscale Vol. 10; no. 9; pp. 4258 - 4266
Main Authors Tang, Jie, Howard, Christopher B, Mahler, Stephen M, Thurecht, Kristofer J, Huang, Leaf, Xu, Zhi Ping
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 2018
Subjects
Animals
Breast cancer
Calcium
Calcium phosphates
Calcium Phosphates - chemistry
Cancer
Cell Line, Tumor
Chemical compounds
Conjugation
Drug Delivery Systems
Folic acid
Humans
Ligands
Lipids
Mice
Mice, Nude
Nanoparticles
Nanoparticles - chemistry
Pharmacology
Platforms
RNA, Small Interfering - administration & dosage
Single-Chain Antibodies
Triple Negative Breast Neoplasms
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Summary: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.
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ISSN:2040-3364
2040-3372
DOI:10.1039/c7nr08644j