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Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer.

Publication ,  Journal Article
Martin, DT; Hoimes, CJ; Kaimakliotis, HZ; Cheng, CJ; Zhang, K; Liu, J; Wheeler, MA; Kelly, WK; Tew, GN; Saltzman, WM; Weiss, RM
Published in: Nanomedicine
November 2013

UNLABELLED: Nearly 40% of patients with non-invasive bladder cancer will progress to invasive disease despite locally-directed therapy. Overcoming the bladder permeability barrier (BPB) is a challenge for intravesical drug delivery. Using the fluorophore coumarin (C6), we synthesized C6-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface modified with a novel cell penetrating polymer, poly(guanidinium oxanorbornene) (PGON). Addition of PGON to the NP surface improved tissue penetration by 10-fold in intravesically-treated mouse bladder and ex vivo human ureter. In addition, NP-C6-PGON significantly enhanced intracellular uptake of NPs compared to NPs without PGON. To examine biological activity, we synthesized NPs that were loaded with the histone deacetylase (HDAC) inhibitor belinostat (NP-Bel-PGON). NP-Bel-PGON exhibited a significantly lower IC50 in cultured bladder cancer cells, and sustained hyperacetylation, when compared to unencapsulated belinostat. Xenograft tumors treated with NP-Bel-PGON showed a 70% reduction in volume, and a 2.5-fold higher intratumoral acetyl-H4, when compared to tumors treated with unloaded NP-PGON. FROM THE CLINICAL EDITOR: These authors demonstrate that PLGA nanoparticles with PGON surface functionalization result in greatly enhanced cell penetrating capabilities, and present convincing data from a mouse model of bladder cancer for increased chemotherapy efficacy.

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Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

November 2013

Volume

9

Issue

8

Start / End Page

1124 / 1134

Location

United States

Related Subject Headings

  • Urothelium
  • Urinary Bladder Neoplasms
  • Urinary Bladder
  • Sulfonamides
  • Polyglactin 910
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Hydroxamic Acids
  • Humans
 

Citation

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Martin, D. T., Hoimes, C. J., Kaimakliotis, H. Z., Cheng, C. J., Zhang, K., Liu, J., … Weiss, R. M. (2013). Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer. Nanomedicine, 9(8), 1124–1134. https://doi.org/10.1016/j.nano.2013.05.017
Martin, Darryl T., Christopher J. Hoimes, Hristos Z. Kaimakliotis, Christopher J. Cheng, Ke Zhang, Jingchun Liu, Marcia A. Wheeler, et al. “Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer.Nanomedicine 9, no. 8 (November 2013): 1124–34. https://doi.org/10.1016/j.nano.2013.05.017.
Martin DT, Hoimes CJ, Kaimakliotis HZ, Cheng CJ, Zhang K, Liu J, et al. Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer. Nanomedicine. 2013 Nov;9(8):1124–34.
Martin, Darryl T., et al. “Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer.Nanomedicine, vol. 9, no. 8, Nov. 2013, pp. 1124–34. Pubmed, doi:10.1016/j.nano.2013.05.017.
Martin DT, Hoimes CJ, Kaimakliotis HZ, Cheng CJ, Zhang K, Liu J, Wheeler MA, Kelly WK, Tew GN, Saltzman WM, Weiss RM. Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer. Nanomedicine. 2013 Nov;9(8):1124–1134.
Journal cover image

Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

November 2013

Volume

9

Issue

8

Start / End Page

1124 / 1134

Location

United States

Related Subject Headings

  • Urothelium
  • Urinary Bladder Neoplasms
  • Urinary Bladder
  • Sulfonamides
  • Polyglactin 910
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Hydroxamic Acids
  • Humans