Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting

Jan 8, 2021Molecular pharmaceutics

Nose Delivery of Temozolomide-Linked Gold Nanoparticles Targeting Brain Tumors with Anti-EphA3

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The anti-EphA3-TMZ@GNPs measure 46.12 ± 2.0 nm and demonstrate significant enhancements in glioma targeting and treatment efficacy.

The system allows bypassing the blood-brain barrier for targeted delivery to glioma cells.
In vitro tests show anti-EphA3-TMZ@GNPs lead to a higher cell apoptosis ratio (54.9%) compared to TMZ (14.1%) in glioma cells.
In TMZ-resistant glioma cells, the IC50 of anti-EphA3-TMZ@GNPs is 18.5-fold lower than that of TMZ (64.06 ± 0.16 μM).
Western blot analysis indicates anti-EphA3-TMZ@GNPs reduce expression of a key DNA repair protein, increasing chemosensitivity.
In vivo studies show that anti-EphA3-TMZ@GNPs extend median survival time to 42 days in glioma-bearing rats.

AI simplified

Glioblastoma multiforme (GBM) is a highly lethal and aggressive tumor of the brain that carries a poor prognosis. Temozolomide (TMZ) has been widely used as a first-line treatment for GBM. However, poor brain targeting, side effects, and drug resistance limit its application for the treatment of GBM. We designed a Temozolomide-conjugated gold nanoparticle functionalized with an antibody against the ephrin type-A receptor 3 (anti-EphA3-TMZ@GNPs) for targeted GBM therapy via intranasal administration. The system can bypass the blood-brain barrier and target active glioma cells to improve the glioma targeting of TMZ and enhance the treatment efficacy, while reducing the peripheral toxicity and drug resistance. The prepared anti-EphA3-TMZ@GNPs were 46.12 ± 2.0 nm and suitable for intranasal administration, which demonstrated high safety to the nasal mucosa in a toxicity assay. In vitro studies showed that anti-EphA3-TMZ@GNPs exhibited significantly enhanced cellular uptake and toxicity, and a higher cell apoptosis ratio has been seen compared with that of TMZ (54.9 and 14.1%, respectively) toward glioma cells (C6). The results from experiments on TMZ-resistant glioma cells (T98G) demonstrated that the ICof anti-EphA3-TMZ@GNPs (64.06 ± 0.16 μM) was 18.5-fold lower than that of TMZ. In addition, Western blot analysis also revealed that anti-EphA3-TMZ@GNPs effectively down-modulated expression of O-methylguanine-DNA methyltransferase and increased chemosensitivity of T98G to TMZ. The antiglioma efficacy in vivo was investigated in orthotopic glioma-bearing rats, and the results demonstrated that the anti-EphA3-TMZ@GNPs prolonged the median survival time to 42 days and increased tumor-cell apoptosis dramatically compared with TMZ. In conclusion, anti-EphA3-TMZ@GNPs could serve as an intranasal drug delivery system for efficacious treatment of GBM. 50 6

Full Text

Full text is available at the source.

View full text ↗

Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief