Glioma targeting peptide modified apoferritin nanocage

Abstract

Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available apoferritin nanocage-based drug delivery system with the modification of GKRK peptide ligand (GKRK-APO). Apoferritin (APO), an endogenous nanosize spherical protein, can specifically bind to brain endothelial cells and glioma cells via interacting with the transferrin receptor 1 (TfR1). GKRK is a peptide ligand of heparan sulfate proteoglycan (HSPG) over-expressed on angiogenesis and glioma, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect of GKRK peptide and parent APO, GKRK-APO displayed higher glioma localization than that of parent APO. After loading with VCR, GKRK-APO showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that GKRK-APO is an important potential drug delivery system for glioma-targeted therapy.

Curcumin-Loaded Nanoparticles with Low-Intensity Focused Ultrasound-Induced Phase Transformation as Tumor-Targeted and pH-Sensitive Theranostic Nanoplatform of Ovarian Cancer

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Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

“…A dual-targeted delivery system (GKRK-APO) made of APO and GKRK peptide ligand, increases the specific targeting to brain endothelial cells and glioma cells and displayed higher glioma localization. Based on the results of the experiments, it has been demonstrated that GKRK-APO loaded with VCR efficiently overcame multiple barriers (e.g., BBB and BBTB) and showed an effective anti-glioma effect in vitro and in vivo [ 128 ]. Another study relates to the Pep-1&borneol-bifunctionalized CMS-loaded micelles (Pep1/Bor/CMS-M) was able to target interleukin-13 receptor overexpressed glioma and penetrate BBB.…”

Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

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