Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

Tzu-Yin Lin, Hongyong Zhang, Juntao Luo, Yuanpei Li, Tingjuan Gao, Primo N Lara, Ralph W deVere White, Kit Lam, Chong-Xian Pan

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19 Citations (Scopus)

Abstract

Background: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells. Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies. Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2± 8. nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P<, 0.01) and nontargeting micelles (1.5×; <, 0.05). Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.

Original languageEnglish (US)
Pages (from-to)2793-2804
Number of pages12
JournalInternational Journal of Nanomedicine
Volume7
DOIs
StatePublished - 2012

Fingerprint

Micelles
Urinary Bladder Neoplasms
Imaging techniques
Dogs
Cells
Therapeutics
Pharmaceutical Preparations
Cholic Acid
Daunorubicin
Drug Delivery Systems
Paclitaxel
Drug delivery
Heterografts
Polyethylene glycols
Coloring Agents
Dyes
Monomers
Ligands
Cell Line

Keywords

  • Bladder cancer-specific peptide
  • Bladder urothelial carcinoma
  • Diagnostic imaging
  • Nanoparticle
  • Targeted therapy

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

@article{fc331e3a21414433aedc7209e5ec3957,
title = "Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer",
abstract = "Background: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells. Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies. Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2± 8. nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P<, 0.01) and nontargeting micelles (1.5×; <, 0.05). Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients. 2012 C{\'a}rdenas et al, publisher and licensee Dove Medical Press Ltd.",
keywords = "Bladder cancer-specific peptide, Bladder urothelial carcinoma, Diagnostic imaging, Nanoparticle, Targeted therapy",
author = "Tzu-Yin Lin and Hongyong Zhang and Juntao Luo and Yuanpei Li and Tingjuan Gao and Lara, {Primo N} and {deVere White}, {Ralph W} and Kit Lam and Chong-Xian Pan",
year = "2012",
doi = "10.2147/IJN.S27734",
language = "English (US)",
volume = "7",
pages = "2793--2804",
journal = "International Journal of Nanomedicine",
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TY - JOUR

T1 - Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

AU - Lin, Tzu-Yin

AU - Zhang, Hongyong

AU - Luo, Juntao

AU - Li, Yuanpei

AU - Gao, Tingjuan

AU - Lara, Primo N

AU - deVere White, Ralph W

AU - Lam, Kit

AU - Pan, Chong-Xian

PY - 2012

Y1 - 2012

N2 - Background: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells. Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies. Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2± 8. nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P<, 0.01) and nontargeting micelles (1.5×; <, 0.05). Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.

AB - Background: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells. Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies. Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2± 8. nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P<, 0.01) and nontargeting micelles (1.5×; <, 0.05). Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.

KW - Bladder cancer-specific peptide

KW - Bladder urothelial carcinoma

KW - Diagnostic imaging

KW - Nanoparticle

KW - Targeted therapy

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