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Updated: Jul 25, 2025
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Rational design of a glycopeptide probe system based on a reconfigurable immune microenvironment
Xin Wang1, Yao Yu1, Limin Zhang1
1Beijing Institute of Technology, Beijing 100081, China. shixianglu@bit.edu.cn.
Abstract:
Glioma is a highly challenging human malignancy and conventional drugs typically exhibit low blood-brain barrier (BBB) permeability as well as poor tumor targeting. To complicate matters further, recent advances in research on oncology have highlighted the dynamic and complex cellular networks within the immunosuppressive tumor microenvironment (TME) that complicate glioma treatment. Therefore, precise and efficient targeting of tumor tissue, whilst reversing immunosuppression, may provide an ideal strategy for the treatment of gliomas. Here, by using the "one-bead-one-component" combinatorial chemistry approach, we designed and screened a peptide that can specifically target brain glioma stem cells (GSCs), which was further engineered into glycopeptide-functionalized multifunctional micelles. We demonstrated that the micelles can carry DOX and effectively penetrate the BBB to achieve targeted killing of glioma cells. Meanwhile, mannose confers a unique tumor immune microenvironment modulating function to the micelles, which can activate the anti-tumor immune response function of tumor-associated macrophages and is expected to be further applied in vivo. This study highlights that glycosylation modification of targeted peptides specific to cancer stem cells (CSCs) may serve as an effective tool to improve the therapeutic outcome of brain tumor patients.
Insights
Researchers developed novel glycopeptide-functionalized micelles to target brain glioma stem cells (GSCs). These micelles effectively cross the blood-brain barrier (BBB), deliver chemotherapy drugs, and modulate the tumor microenvironment for improved glioma treatment.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Glioma presents significant treatment challenges due to poor drug penetration of the blood-brain barrier (BBB) and an immunosuppressive tumor microenvironment (TME).
- Targeting glioma stem cells (GSCs) and modulating the TME are crucial for effective glioma therapy.
Purpose of the Study:
- To design and develop a novel drug delivery system for targeted glioma treatment.
- To engineer multifunctional micelles capable of crossing the BBB, targeting GSCs, and modulating the TME.
Main Methods:
- Utilized a "one-bead-one-component" combinatorial chemistry approach to screen for a GSC-targeting peptide.
- Engineered the peptide into glycopeptide-functionalized multifunctional micelles loaded with doxorubicin (DOX).
- Investigated the micelles' ability to penetrate the BBB, target glioma cells, and modulate macrophage activity.
Main Results:
- Successfully designed and synthesized glycopeptide-functionalized micelles that specifically target GSCs.
- Demonstrated effective BBB penetration and targeted delivery of DOX to glioma cells.
- Showcased the mannose-mediated immune-modulating function, activating anti-tumor responses in tumor-associated macrophages.
Conclusions:
- Glycosylation modification of targeted peptides offers a promising strategy for enhancing brain tumor therapy.
- Multifunctional micelles represent a viable platform for overcoming BBB limitations and improving glioma treatment outcomes.
- This approach holds potential for future in vivo applications in treating brain tumors.
