Dual targeting of solid lipid nanoparticles grafted with 83-14 MAb and anti-EGF receptor for malignant brain tumor therapy

Abstract

Aims: Solid lipid nanoparticles (SLNs) conjugated with surface 83-14 monoclonal antibody (8314MAb) and anti-epithelial growth factor receptor (AEGFR) were synthesized and applied to permeate the blood-brain barrier (BBB) and inhibit the growth of glioblastoma multiforme (GBM).

Main methods: 8314MAb and AEGFR were crosslinked on SLNs to carry etoposide (ETP) across human brain-microvascular endothelial cells (HBMECs) and to treat U87MG cells.

Key findings: An increase in the 8314MAb concentration increased the permeability for propidium iodide (PI) and ETP across the BBB, however, decreased the 8314MAb grafting efficiency and transendothelial electrical resistance of the monolayer of HBMECs. In addition, an increase in the AEGFR concentration enhanced the viability of HBMECs and human astrocytes (HAs), however, reduced the AEGFR grafting efficiency and ETP release rate. An incorporation of both 8314MAb and AEGFR increased the particle size, however, decreased the zeta potential, ETP release rate, and viability of HBMECs and HAs.

Significance: The conjugation of 8314MAb and AEGFR on ETP-loaded SLNs can be a promising strategy to deliver antitumor ETP to the brain and restrain the propagation of GBM.

Keywords: 83-14 monoclonal antibody; Anti-epithelial growth factor receptor; Blood–brain barrier; Etoposide; Glioblastoma multiforme; Solid lipid nanoparticle.