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

Jie Tang; Christopher B. Howard; Stephen M. Mahler; Kristofer J. Thurecht; Leaf Huang; Zhi Ping Xu

doi:10.1039/c7nr08644j

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

Jie Tang, Christopher B. Howard, Stephen M. Mahler, Kristofer J. Thurecht, Leaf Huang, Zhi Ping Xu

Research output: Contribution to journal › Article › Research › peer-review

68 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	4258-4266
Number of pages	9
Journal	Nanoscale
Volume	10
Issue number	9
DOIs	https://doi.org/10.1039/c7nr08644j
Publication status	Published - 2018
Externally published	Yes

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10.1039/c7nr08644j

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@article{fb1b946e2ae2447c884f40c1f59b3a21,

title = "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",

abstract = "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.",

author = "Jie Tang and Howard, {Christopher B.} and Mahler, {Stephen M.} and Thurecht, {Kristofer J.} and Leaf Huang and Xu, {Zhi Ping}",

note = "Funding Information: This work was financially supported by the Australian Research Centre (ARC) Future Fellowship (FT120100813), the ARC DP grant (DP170104643), Chinese Scholarship Council (CSC), and NIH grants CA198999 and DK100664. The authors acknowledged the facilities and the assistance of the Queensland Node of the Australian National Fabrication Facility (ANFF-Q), the University of Queensland. Publisher Copyright: {\textcopyright} 2018 The Royal Society of Chemistry.",

year = "2018",

doi = "10.1039/c7nr08644j",

language = "English",

volume = "10",

pages = "4258--4266",

journal = "Nanoscale",

issn = "2040-3364",

publisher = "The Royal Society of Chemistry",

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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. / Tang, Jie; Howard, Christopher B.; Mahler, Stephen M. et al.
In: Nanoscale, Vol. 10, No. 9, 2018, p. 4258-4266.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - 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

AU - Tang, Jie

AU - Howard, Christopher B.

AU - Mahler, Stephen M.

AU - Thurecht, Kristofer J.

AU - Huang, Leaf

AU - Xu, Zhi Ping

N1 - Funding Information: This work was financially supported by the Australian Research Centre (ARC) Future Fellowship (FT120100813), the ARC DP grant (DP170104643), Chinese Scholarship Council (CSC), and NIH grants CA198999 and DK100664. The authors acknowledged the facilities and the assistance of the Queensland Node of the Australian National Fabrication Facility (ANFF-Q), the University of Queensland. Publisher Copyright: © 2018 The Royal Society of Chemistry.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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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U2 - 10.1039/c7nr08644j

DO - 10.1039/c7nr08644j

M3 - Article

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AN - SCOPUS:85042866969

SN - 2040-3364

VL - 10

SP - 4258

EP - 4266

JO - Nanoscale

JF - Nanoscale

IS - 9

ER -

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

Abstract

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