Related Experiment Video
Updated: Mar 2, 2026
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple Barriers
Huitong Ruan1, Xishan Chen1, Cao Xie1
1Key Laboratory of Smart Drug Delivery of the Ministry of Education (Fudan University), & Department of Pharmaceutics, School of Pharmacy, Fudan University , Shanghai 201203, P.R. China.
Abstract:
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells. As expected, sRGD-modified micelles were able to penetrate the in vitro BBB model while retaining the glioma targeted capability. The results of the in vivo imaging studies further revealed that this nanocarrier could not only efficiently transverse the intact BBB of normal mice, but also could specifically target glioma cells of intracranial glioma-bearing nude mice. Furthermore, Paclitaxel-loaded sRGD-modified micelles exhibited improved antiglioma efficacy in vitro and significantly prolonged survival time of glioma-bearing nude mice. Overall, this sRGD peptide showed potency for glioma-targeted drug delivery by overcoming multiple barriers.
Insights
Researchers developed a novel stapled RGD peptide (sRGD) to overcome the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) for targeted glioma drug delivery, significantly improving treatment efficacy and survival rates.
Area of Science:
- Nanotechnology in oncology
- Central nervous system drug delivery
- Molecular targeting of gliomas
Background:
- Malignant glioma is an aggressive brain tumor with poor prognosis.
- The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) impede therapeutic agent penetration.
- Effective drug delivery strategies are crucial for improving glioma treatment outcomes.
Purpose of the Study:
- To design a novel cyclic RGD ligand (sRGD) for enhanced BBB and BBTB penetration.
- To evaluate the capability of sRGD-modified micelles for targeted glioma drug delivery.
- To assess the in vivo efficacy of sRGD-mediated nanocarriers in glioma-bearing mice.
Main Methods:
- Design of an all-hydrocarbon stapled RGD peptide (sRGD).
- Modification of micelles with sRGD for improved BBB penetration and glioma targeting.
- In vitro and in vivo studies using BBB models and intracranial glioma-bearing mice.
- Evaluation of drug-loaded sRGD micelles for anti-glioma efficacy and survival.
Main Results:
- sRGD-modified micelles successfully penetrated an in vitro BBB model.
- In vivo imaging confirmed efficient BBB and BBTB traversal and specific glioma cell targeting.
- Paclitaxel-loaded sRGD micelles demonstrated enhanced anti-glioma efficacy and prolonged survival in mice.
Conclusions:
- The sRGD peptide effectively overcomes the BBB and BBTB, facilitating targeted glioma drug delivery.
- sRGD-modified nanocarriers represent a promising strategy for improving malignant glioma treatment.
- This approach holds potential for overcoming multiple biological barriers in brain tumor therapy.
