Enhanced Targeted Delivery of Cyclodextrin-Based Supermolecules by Core-Shell Nanocapsules for Magnetothermal Chemotherapy

Macromol Biosci. 2016 Sep;16(9):1273-86. doi: 10.1002/mabi.201600131. Epub 2016 Jun 21.

Abstract

In this study, double-emulsion capsules (DECs) capable of concealing drug-incorporated targeted-supermolecules are developed to achieve "on-demand" supermolecule release and enhanced sequential targeting for magneto-chemotherapy. These water-in-oil-in-water DECs less than 200 nm in diameter are synthesized using a single component of PVA (polyvinyl alcohol) polymer and the magnetic nanoparticles, which are capable of encapsulating large quantities of targeted supermolecules composed of palitaxel-incorporated beta-cyclodextrin decorated by hyaluronic acid (HA, a CD44-targeting ligand) in the watery core. The release profiles (slow, sustained and burst release) of the targeted supermolecules can be directly controlled by regulating the high-frequency magnetic field (HFMF) and polymer conformation without sacrificing the targeting ability. Through an intravenous injection, the positive targeting of the supermolecules exhibited a 20-fold increase in tumor accumulation via the passive targeting and delivery of DECs followed by positive targeting of the supermolecules. Moreover, this dual-targeting drug-incorporated supermolecular delivery vehicle at the tumor site combined with magneto-thermal therapy suppressed the cancer growth more efficiently than treatment with either drug or supermolecule alone.

Keywords: cancer targeting; drug delivery; magnetic nanoparticle; supermolecule; thermal chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Delivery Systems / methods*
  • Emulsions / chemistry
  • Endocytosis
  • HeLa Cells
  • Humans
  • Hyaluronic Acid / chemical synthesis
  • Hyaluronic Acid / chemistry
  • Hyperthermia, Induced / methods*
  • Kinetics
  • MCF-7 Cells
  • Magnetics / methods*
  • Mice, Nude
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Particle Size
  • Staining and Labeling
  • X-Ray Diffraction
  • Xenograft Model Antitumor Assays
  • beta-Cyclodextrins / chemical synthesis
  • beta-Cyclodextrins / chemistry*

Substances

  • Antineoplastic Agents
  • Emulsions
  • Nanocapsules
  • beta-Cyclodextrins
  • Hyaluronic Acid