Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate

Angew Chem Int Ed Engl. 2009;48(16):2949-54. doi: 10.1002/anie.200805133.

Abstract

A polymer therapeutic designed for combination anticancer and antiangiogenic therapy inhibited the proliferation of prostate carcinoma cells and the proliferation, migration, and tube-formation of endothelial cells. The nanoconjugate was formed from an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, the bisphosphonate alendronate (for bone targeting), and the chemotherapy agent paclitaxel (PTX), which is cleaved by cathepsin B (see scheme).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemical synthesis
  • Acrylamides / chemistry*
  • Alendronate / chemistry
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Bridged-Ring Compounds / chemistry
  • Cathepsin B / metabolism
  • Cells, Cultured
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / chemistry
  • Polymers / chemistry
  • Taxoids / chemistry
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Acrylamides
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • HPMA copolymer-PTX-FK-ALN conjugate
  • Polymers
  • Taxoids
  • Vascular Endothelial Growth Factor A
  • taxane
  • Cathepsin B
  • Paclitaxel
  • N-(2-hydroxypropyl)methacrylamide
  • Alendronate