The destructive spontaneous ingression of tunable silica nanosheets through cancer cell membranes

Abstract

Robust inorganic graphene analogues with atomic level sharp edges have seldom been investigated to decipher the interaction of two-dimensional materials with the cell membrane. Silica nanosheets (NSs) with four different thicknesses between 2.9 nm and 11.1 nm were synthesized by microwave irradiation and these colloidal NSs were able to spontaneously penetrate the cell membrane leaving membrane perforations at their sites of entry. The NS-ingression was most effective with the thinnest NSs, when studied in vitro. The atomistic details of the NS-membrane interaction were revealed by molecular dynamics (MD) simulations, which showed that the extraction of phospholipids was most favored when NSs were oriented vertically with respect to the membrane surface. While the folic acid modified NSs demonstrated a riveting tendency to penetrate the cancer cell membrane, co-modification with doxorubicin (DOX) unexpectedly reduced their capability. Migrating away from a conventional drug delivery approach, here we show that silica NSs can kill cancer cells primarily by mechanical scalpelling. Targeted ingress could be achieved through antibody conjugation on the NSs and thus only cancerous HeLa cells are affected by this treatment, leaving the normal HEK-293 cells intact. This destructive ingress through limited oxidative stress offers a previously unexplored route to treat fatal diseases without the necessity of transporting expensive drugs or radiation therapy, thereby bypassing deleterious side effects on healthy cells.