Cardiolipin for Enhanced Cellular Uptake and Cytotoxicity of Thermosensitive Liposome-Encapsulated Daunorubicin toward Breast Cancer Cell Lines

Int J Mol Sci. 2022 Oct 4;23(19):11763. doi: 10.3390/ijms231911763.

Abstract

Daunorubicin (DNR) and cardiolipin (CL) were co-delivered using thermosensitive liposomes (TSLs). 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-myristoyl-2-stearoyl-sn-glycero-3-phosphocholine (MSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] or DSPE-mPEG (2000) and CL were used in the formulation of liposomes at a molar ratio of 57:40:30:3:20, respectively. CL forms raft-like microdomains that may relocate and change lipid organization of the outer and inner mitochondrial membranes. Such transbilayer lipid movement eventually leads to membrane permeabilization. TSLs were prepared by thin-film hydration (drug:lipid ratio 1:5) where DNR was encapsulated within the aqueous core of the liposomes and CL acted as a component of the lipid bilayer. The liposomes exhibited high drug encapsulation efficiency (>90%), small size (~115 nm), narrow size distribution (polydispersity index ~0.12), and a rapid release profile under the influence of mild hyperthermia. The liposomes also exhibited ~4-fold higher cytotoxicity against MDA-MB-231 cells compared to DNR or liposomes similar to DaunoXome® (p < 0.001). This study provides a basis for developing a co-delivery system of DNR and CL encapsulated in liposomes for treatment of breast cancer.

Keywords: breast cancer; cardiolipin; daunorubicin; liposomes; thermosensitive.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Cardiolipins
  • Cholesterol
  • Daunorubicin / pharmacology
  • Female
  • Humans
  • Lipid Bilayers
  • Liposomes*
  • MCF-7 Cells
  • Phosphorylcholine
  • Polyethylene Glycols

Substances

  • Cardiolipins
  • Lipid Bilayers
  • Liposomes
  • Phosphorylcholine
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol
  • Cholesterol
  • Daunorubicin

Grants and funding

Authors (H.A., R.J.B., R.D.A.) acknowledge the funding support from Auburn University Intramural Grant Program (AU-IGP), and Auburn University Research Initiative in Cancer (AURIC). The manuscript has been supported in part by Susan G. Komen Breast Cancer Foundation (CCR18548498 to A.K.T) and the Department of Defense (W81XWH210053 to A.K.T.).