Taxane-Grafted Metal-Oxide Nanoparticles as a New Theranostic Tool against Cancer: The Promising Example of Docetaxel-Functionalized Titanate Nanotubes on Prostate Tumors

Adv Healthc Mater. 2017 Aug;6(16). doi: 10.1002/adhm.201700245. Epub 2017 May 18.

Abstract

The combination of anticancer drugs and metal oxide nanoparticles is of great interest in cancer nanomedicine. Here, the development of a new nanohybrid, titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are conjugated by covalent linkages. Unlike most nanoparticles currently being developed for biomedical purposes, TiONts present a needle-shaped morphology. The surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero-bifunctional polymer (polyethylene glycol) to create well-dispersed and biocompatible nanovectors. The prefunctionalized surface of this scaffold has valuable attachments to graft therapeutic agents (DTX in our case) as well as chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have demonstrated that the association between TiONts and DTX shows cytotoxic activity against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts without DTX do not. Finally, the first in vivo tests with intratumoral injections show that more than 70% of TiONts nanovectors are retained within the tumor for at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is significantly slower than that in mice receiving free DTX. This nanohybrid can thus become a promising new tool in biomedicine to fight against prostate cancer.

Keywords: docetaxel; nanocarriers; prostate cancer; titanate nanotubes; vectorization.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Cell Line, Tumor
  • Docetaxel
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Stability
  • Humans
  • Male
  • Metal Nanoparticles / chemistry*
  • Mice
  • Mice, Nude
  • Oxides / chemistry
  • Particle Size
  • Prostatic Neoplasms / metabolism*
  • Taxoids* / chemistry
  • Taxoids* / pharmacokinetics
  • Theranostic Nanomedicine / methods*
  • Tissue Distribution
  • Titanium / chemistry
  • Titanium / pharmacokinetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Oxides
  • Taxoids
  • Docetaxel
  • Titanium