Theranostic micelles combined with multiple strategies to effectively overcome multidrug resistance

Nanomedicine (Lond). 2018 Jul;13(13):1517-1533. doi: 10.2217/nnm-2017-0393.

Abstract

Aim: To develop precise targeting and versatile Fe3O4@SiO2-P123/PTX-ZnPc nanoparticles (FSP-PTX-ZnPc NPs) to reverse paclitaxel (PTX)-induced multidrug resistance in breast cancer.

Materials & methods: PTX and zinc (II) phthalocyanine (ZnPc) co-loaded FSP-PTX-ZnPc NPs were designed. The resulting multifunctional NPs were evaluated systematically in vitro and in vivo, and the mechanism of drug-resistance reversal was investigated.

Results: The NPs enhanced drug uptake in MCF-7/PDR cells by increasing drug solubility and impairing P-glycoprotein efflux. Additionally, magnetic targeting and enhanced permeation and retention (EPR) effect enhanced drug accumulation in tumor, facilitating the chemotherapeutic and photodynamic therapy effects. Moreover, FSP-PTX-ZnPc NPs could penetrate the blood-brain barrier, a desirable trait for brain disease therapy.

Conclusion: The multifunctional FSP-PTX-ZnPc NPs are an effective tool for overcoming drug resistance in breast cancer.

Keywords: breast cancer; drug resistance; magnetic targeting; nanoparticles; paclitaxel; photodynamic therapy; zinc(II) phthalocyanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / adverse effects
  • Albumins / therapeutic use*
  • Blood-Brain Barrier / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Drug Delivery Systems
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Ferric Compounds / chemistry
  • Ferric Compounds / pharmacology
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology
  • MCF-7 Cells
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Micelles
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use*
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / pharmacology*
  • Theranostic Nanomedicine

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Ferric Compounds
  • Indoles
  • Micelles
  • Organometallic Compounds
  • ferric oxide
  • zinc(II) phthalocyanine trisulfonic acid
  • Silicon Dioxide
  • Paclitaxel