A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance

Int J Nanomedicine. 2017 Nov 1:12:8043-8056. doi: 10.2147/IJN.S148273. eCollection 2017.

Abstract

Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C18 as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment. Compared with MCF-7 cells, the DAS and PTX co-loaded redox-sensitive micelle (SS-PDNPs) showed stronger cytotoxicity and a more improving intracellular drug concentration than other drug formulations in MCF-7/ADR cells. In summary, the results suggested that the simple co-delivery micelles of PTX and DAS possessed significant potential to overcome drug resistance in cancer therapy.

Keywords: co-delivery; dasatinib; overcoming multidrug resistant; paclitaxel; redox responsive.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Dasatinib / administration & dosage*
  • Drug Liberation
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • MCF-7 Cells
  • Micelles
  • Oxidation-Reduction
  • Paclitaxel / administration & dosage*
  • Polyethylene Glycols / chemistry

Substances

  • Micelles
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol
  • Paclitaxel
  • Dasatinib