A Magnetic-Responsive Biomimetic Nanosystem Coated with Glioma Stem Cell Membranes Effectively Targets and Eliminates Malignant Gliomas.

Abstract

Glioblastoma multiforme (GBM) is among the most challenging malignant brain tumors, making the development of new treatment strategies highly necessary. Glioma stem cells (GSCs) markedly contribute to drug resistance, radiation resistance, and tumor recurrence in GBM. The therapeutic potential of nanomaterials targeting GSCs in GBM urgently needs to be explored. A magnetic-responsive biomimetic nanosystem (FDPM), coated with glioma stem cell membranes (CMs), was designed for the targeted eradication of GSCs as well as their associated tumor cells. Identified nanobodies were extensively characterized with various assays. The application tests on nanomaterials were conducted in vitro and in vivo. The tumor-suppressive effects of the nanosystem were evaluated in vitro and in vivo. FDPM can be artificially directed under magnetic guidance while inheriting various biological functions from CM. Upon intravenous injection, FDPM was drawn to the tumor site by magnetic attraction, where it could cross the blood-brain barrier aided by CM. Its homologous targeting ability originates from active proteins on CM, enabling it to specifically target GSCs and related tumor cells. The encapsulated doxorubicin (DOX) within the nanoparticle then destroyed these tumor cells. FDPM demonstrated excellent biocompatibility and tumor-targeting efficiency, effectively targeting malignant gliomas initiated by GSCs. FDPM significantly reduced tumor cells, inhibited tumor growth, and notably extended the survival of glioma-bearing nude mice. The findings position FDPM as a promising nanoplatform to target GSCs and related tumor cells for improving the therapeutic effect of glioma.