In Vivo Evaluation of Reduction-Responsive Alendronate-Hyaluronan-Curcumin Polymer-Drug Conjugates for Targeted Therapy of Bone Metastatic Breast Cancer

Mol Pharm. 2018 Jul 2;15(7):2764-2769. doi: 10.1021/acs.molpharmaceut.8b00266. Epub 2018 Jun 1.

Abstract

Many cancers, such as human breast cancer and lung cancer, easily metastasize to bones, leading to the formation of secondary tumors in advanced stages. On the basis of the CD44-targeted effect of oHA and the bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nanomicelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN-oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction. The CUR-loaded ALN-oHA-S-S-CUR micelles markedly inhibited the tumor growth. So the CUR-loaded ALN-oHA-S-S-CUR micelles constitute a promising drug delivery system for bone tumor therapy.

Keywords: CD44 receptor; bone tumor therapy; drug delivery; polymer-drug conjugates; reduction-responsive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / chemistry
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Curcumin / administration & dosage*
  • Curcumin / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / chemistry
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Nude
  • Micelles
  • Oxidation-Reduction
  • Particle Size
  • Polymers / chemistry
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • CD44 protein, human
  • Drug Carriers
  • Hyaluronan Receptors
  • Micelles
  • Polymers
  • Hyaluronic Acid
  • Curcumin
  • Alendronate