Targeted delivery of cisplatin to tumor xenografts via the nanoparticle component of nano-diamino-tetrac

Nanomedicine (Lond). 2017 Feb;12(3):195-205. doi: 10.2217/nnm-2016-0315. Epub 2017 Jan 19.

Abstract

Aim: Nano-diamino-tetrac (NDAT) targets a receptor on integrin αvβ3; αvβ3 is generously expressed by cancer cells and dividing endothelial cells and to a small extent by nonmalignant cells. The tetrac (tetraiodothyroacetic acid) of NDAT is covalently bound to a poly(lactic-co-glycolic acid) nanoparticle that encapsulates anticancer drugs. We report NDAT delivery efficiency of cisplatin to agent-susceptible urinary bladder cancer xenografts.

Materials & methods: Cisplatin-loaded NDAT (NDAT-cisplatin) was administered to xenograft-bearing nude mice. Tumor size response and drug content were measured.

Results: Intratumoral drug concentration was up to fivefold higher (p < 0.001) in NDAT-cisplatin-exposed lesions than with conventional systemic administration. Tumor volume reduction achieved was NDAT-cisplatin > NDAT without cisplatin > cisplatin alone.

Conclusion: NDAT markedly enhances cisplatin delivery to urinary bladder cancer xenografts and increases drug efficacy.

Keywords: NDAT; cisplatin; integrin; nanotetrac; tetraiodothyroacetic acid; urinary bladder carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin / administration & dosage*
  • Cisplatin / chemistry
  • Cisplatin / pharmacology
  • Drug Delivery Systems
  • Drug Liberation
  • Female
  • Heterografts
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Lactic Acid / chemistry*
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Neoplasm Transplantation
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Particle Size
  • Polyglactin 910
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Surface Properties
  • Thyroxine / analogs & derivatives
  • Urinary Bladder Neoplasms / drug therapy

Substances

  • ASCC2 protein, human
  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • Nuclear Proteins
  • nano-diamino-tetrac
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyglactin 910
  • Cisplatin
  • Thyroxine