Carbon nanotube-coated recombinant human surfactant protein D reduces cell viability in an ovarian cancer cell line, SKOV3, and modulates mTOR pathway and pro-inflammatory cytokine response

Abstract

Nanoparticles such as carbon nanotubes (CNTs) have various clinical and diagnostic applications as utilised for imaging and drug delivery. Therapeutic proteins/peptides can be loaded on CNT coronas to specifically hit immune cells in overdrive or uncontrolled malignant cells. Previously, it was reported that a recombinant version of human surfactant protein D (rfhSP-D) containing trimeric C-type lectin domains induced apoptosis in several tumour cells/cell lines, including SKOV3, which is an ovarian tumour cell line. Solid-phase rfhSP-D coated on a microtiter plate is considerably more potent in inducing apoptosis in breast tumour cells. We have immobilised highly purified, endotoxin-free rfhSP-D on CNTs and assessed its antiproliferative effect on SKOV3 cells. Biotinylated rfhSP-D-CNTs were phagocytosed by SKOV3 cells, followed by apoptosis in a time-dependent manner. Gene expression analysis revealed compromised mTOR complex as a mechanism of apoptosis. When rfhSP-D-CNTs were added to a culture system of SKOV3 cells, it produced a highly proinflammatory immune response that is likely anti-tumorigenic. Thus, rfhSP-D-CNT seems a worthwhile nanocarrier for testing in vivo using an animal model of orthotopic ovarian cancer.