EGFR/EGFRvIII Dual-Targeting Peptide-Mediated Drug Delivery for Enhanced Glioma Therapy

Abstract

Tumor-homing peptides have been widely used to mediate active targeted drug delivery. l-AE is a reported targeting peptide demonstrating high binding affinity to epidermal growth factor receptor (EGFR) and mutation variant III (EGFRvIII) overexpressed on neovasculature, vasculogenic mimicry, tumor cells, and tumor stem cells. To improve its proteolytic stability, a d-peptide ligand (termed d-AE, the enantiomer of l-AE) was developed. d-AE was confirmed to bind receptors EGFR and EGFRvIII with targeting capability comparable to l-AE. In vivo biodistribution demonstrated the superiority of d-AE in prolonged circulation and enhanced intratumoral accumulation. Furthermore, stabilized peptide modification endowed micelles higher transcytosis efficiency and penetrating capability on blood-brain tumor barrier/U87 tumor spheroids coculture model. When paclitaxel (PTX) was loaded, d-AE-micelle/PTX demonstrated excellent antitumor effect in comparison to Taxol, micelle/PTX, and l-AE-micelle/PTX. These findings indicated that the multitargeted drug delivery system enabled by d-AE ligand provides a promising way for glioma therapy.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting

“…A nanoprobe for the multimodal imaging of EGFRvIII overexpression in glioblastoma was constructed in the study. Compared with the EGFRvIII-antibody-functionalized iron oxide nanoparticles after convection-enhanced delivery (CED) to target EGFRvIII [35] and fluorescent-silica-coated iron oxide nanoparticles to target tumor-associated macrophages [36] and D-AE-peptide-modified micelles as a multitarget drug delivery system [37], the benefits of the nanoprobe in this study are described as follows. First, the nanoprobe has a diameter of around 100 nm and can directly pass through the blood–tumor barrier.…”

“…Lee and co-workers also showed that combining MRI with fluorescent imaging by using fluorescent silica-coated iron oxide nanoparticles has potential application in GBM treatment for improved intraoperative staging and enhanced radical surgery [36]. In addition, Mao and co-workers have reported the multitargeted drug delivery system by a d-peptide ligand (d-AE) based EGFRvIII targeting strategy, which provides a promising path for glioma therapy [37].…”

<p>Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours</p>

“…Given that the "immune privilege" of the brain is no more a retained concept, also the recent advances in immunotherapy strategies offer new opportunities for a synergistic [186] (Continued) [195] (Continued) combination of cell therapy with chemotherapeutic drug delivery systems, in order to target brain tumours. 124 For example, the combination of dendritic cell-targeted vaccines with nanoparticles loaded with anticancer drugs should lead to a superior anticancer activity.…”

<p>Advances and Prospects of Vasculogenic Mimicry in Glioma: A Potential New Therapeutic Target?</p>

“…Liposomes or micelles possess a high binding capacity for receptors and demonstrate superiority in tumor-homing imaging. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] This type of treatment is expected to become a new direction for the treatment of glioma. 58…”