Mild microwave activated, chemo-thermal combinational tumor therapy based on a targeted, thermal-sensitive and magnetic micelle

Biomaterials. 2017 Jul:131:36-46. doi: 10.1016/j.biomaterials.2017.03.048. Epub 2017 Mar 30.

Abstract

The development of combinational anti-tumor therapy is of great value. Here, the thermal-sensitive and hepatic tumor cell targeting peptide-A54 modified polymer, A54-poly(ethylene glycol)-g-poly(acrylamide-co-acrylonitrile) (A54-PEG-g-p(AAm-co-AN)) can self-assemble into an 80 nm-sized micelle, which shows a thermal-sensitive behavior with an upper critical solution temperature (UCST) of 43 °C. This self-assembled and targeted A54-PEG-g-p(AAm-co-AN) micelle can co-encapsulate anti-tumor drug doxorubicin (DOX) and magnetic nanoparticles (MNPs) taking advantage of the hydrophobic core of the core-shell micellar structure, when the temperature is lower than 43 °C. A much higher accumulation of the MNPs@A54-PEG-g-p(AAm-co-AN) to the tumor navigated by the A54 targeting peptide is achieved. Due to the thermal-agent effect of the accumulated MNPs in tumor, the mild microwave (8 W) applied afterwards specifically elevates the local tumor temperature by 13 °C, compared to 6 °C without MNPs accumulation in 30 min. The greater temperature rise resulted from the thermal-agent effect of MNPs doesn't only activate the drug release inside tumor cells, but also achieve an augmented hyperthermia. A mild microwave activated, chemo-thermal combinational tumor therapy is thus developed.

Keywords: Chemo-thermal combinational therapy; Magnetic nanoparticles; Microwave hyperthermia therapy; Targeted drug delivery; UCST.

MeSH terms

  • Acrylic Resins / chemistry
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Delayed-Action Preparations / chemistry*
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use*
  • Female
  • Humans
  • Hyperthermia, Induced
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / therapeutic use*
  • Magnetite Nanoparticles / ultrastructure
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles*
  • Microwaves
  • Peptides / chemistry
  • Polyethylene Glycols / chemistry

Substances

  • Acrylic Resins
  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Magnetite Nanoparticles
  • Micelles
  • Peptides
  • Polyethylene Glycols
  • Doxorubicin
  • polyacrylamide