Ferritin Nanocarrier Traverses the Blood Brain Barrier and Kills Glioma

Abstract

Over the last decades, considerable efforts have been put into developing active nanocarrier systems that cross the blood brain barrier (BBB) to treat brain-related diseases such as glioma tumors. However, to date none have been approved for clinical usage. Here, we show that a human H-ferritin (HFn) nanocarrier both successfully crosses the BBB and kills glioma tumor cells. Its principle point of entry is the HFn receptor (transferrin receptor 1), which is overexpressed in both BBB endothelial cells (ECs) and glioma cells. Importantly, we found that HFn enters and exits the BBB via the endosome compartment. In contrast, upon specifically targeting and entering glioma cells, nearly all of the HFn accumulated in the lysosomal compartment, resulting in the killing of glioma tumor cells, with no HFn accumulation in the surrounding healthy brain tissue. Thus, HFn is an ideal nanocarrier for glioma therapy and possesses the potential to serve as a therapeutic approach against a broad range of central nervous system diseases.

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

“…RMT is the most commonly adopted strategy, which involves the binding of target ligands conjugated onto the nanoparticle to corresponding receptors expressed on the surface of brain endothelial cells to improve the delivery of loaded therapeutic agents into the brain. [ 2,11–13 ] Recently, several target ligands including transferrin, lactoferrin, and angiopep‐2 have been exploited to cross BBB by receptor‐mediated transcytosis. [ 12,14–16 ] However, the less than 1.0% of the brain accumulation rate of these nanoparticles cannot meet the requirements of clinical use, which is due to the low efficiency of ligand upload on nanoparticles, weak binding ability with receptors, and the competition of high concentration of endogenous ligands in the blood.…”

“…[ 2,11–13 ] Recently, several target ligands including transferrin, lactoferrin, and angiopep‐2 have been exploited to cross BBB by receptor‐mediated transcytosis. [ 12,14–16 ] However, the less than 1.0% of the brain accumulation rate of these nanoparticles cannot meet the requirements of clinical use, which is due to the low efficiency of ligand upload on nanoparticles, weak binding ability with receptors, and the competition of high concentration of endogenous ligands in the blood. [ 5,6 ] Therefore, it is still challenging to develop a strategy to endow nanoparticles with essential functions such as BBB‐crossing ability, high tumor accumulation, and immune escape for the treatment of brain diseases.…”

<p>Slp-coated liposomes for drug delivery and biomedical applications: potential and challenges</p>

“…59 Transferrin is generally used to allow liposomes or other nanoparticles to cross the blood-brain barrier, achieving delivery to central nervous system. [60][61][62] Other functional proteins or peptides, such as EGF and RGD, also support targeting delivery. Furthermore, membrane-active peptide 63,64 and cell-penetrating peptide 65,66 facilitate the intracellular delivery of liposomes.…”

Intelligent Nanocomposites with Intrinsic Blood–Brain‐Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma

“…to the cerebrum, thereby compromising the outcomes of diagnosis and therapy . With the increasing development of nanomaterials, receptor‐mediated transcytosis (RMT) has become one of the most promising protocols to overcome the BBB through receptors that are highly expressed on BBB endothelial cells, among which transferrin receptor (TfR) is a promising candidate . Moreover, TfR is also present in substantial quantities on GBM cells due to their high proliferation rate and iron demand .…”