Pluronic P123 modified nano micelles loaded with doxorubicin enhanced tumor-suppressing effect on drug-resistant breast cancer cells

Aging (Albany NY). 2020 May 12;12(9):8289-8300. doi: 10.18632/aging.103138. Epub 2020 May 12.

Abstract

Objective: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells.

Results: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1.

Conclusions: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms.

Methods: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.

Keywords: P-glycoprotein; Pluronic P123 modification; breast cancer; multi-drug resistance; nano micelles.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Micelles
  • Poloxalene / administration & dosage*

Substances

  • Antibiotics, Antineoplastic
  • Micelles
  • pluronic block copolymer P123
  • Doxorubicin
  • Poloxalene