INTERNATIONAL CONGRESS OF
CancerGenetics
Peptide-Based Nanocarriers for Overcoming the Blood-Brain Barrier in Glioblastoma Therapy
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Ali Karimi-Jashni,1,* Negin Karami,2
1. Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
2. Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
- Introduction: Glioblastoma (GBM) is recognized as the most aggressive primary brain tumor, characterized by rapid cellular proliferation, widespread infiltration into adjacent brain tissues, and a notably poor prognosis with limited overall survival. One of the main challenges in treating GBM is the presence of the blood-brain barrier (BBB), a highly selective endothelial interface that restricts the passage of chemotherapeutic and biologic agents into the central nervous system. Successfully bypassing or modulating this barrier is critical for enhancing drug delivery efficiency and improving therapeutic outcomes in GBM patients. Peptide-based nanocarriers have lately garnered significant attention as they offer excellent biocompatibility, customizable architectures, and the ability to specifically interact with receptors expressed on BBB endothelial cells and glioblastoma tumor cells, facilitating targeted delivery.
- Methods: This review systematically examines the most extensively studied peptide-based nanocarriers utilized for GBM therapy. Specifically, it focuses on Angiopep-2, which targets the LRP1 receptor; RGD peptides that bind integrin receptors; TAT, a well-known cell-penetrating peptide; and peptides targeting the transferrin receptor. The mechanisms enabling BBB crossing, tumor homing, and intracellular drug release were assessed based on comprehensive analysis of preclinical animal studies as well as available clinical trial data. Key parameters such as receptor selectivity, efficiency of cellular uptake, pharmacokinetic profiles, biodistribution patterns, and therapeutic efficacy were compared to delineate the strengths and limitations inherent to each peptide platform.
- Results: Peptides with receptor-targeting capabilities, including Angiopep-2 and RGD, significantly enhance the delivery of therapeutic agents to GBM by promoting receptor-mediated transcytosis across the BBB and improving penetration into tumor tissue. Angiopep-2-based drug conjugates, notably ANG1005, have advanced into early-phase clinical trials, showing promising safety and efficacy, thus supporting their translational potential. Cell-penetrating peptides, such as TAT, ensure efficient intracellular transport and broad drug distribution but lack inherent tumor specificity. Transferrin receptor-targeting peptides utilize receptor-mediated endocytosis pathways to facilitate transport across the BBB and accumulation in glioma cells. Collectively, these peptide-based nanocarriers increase drug bioavailability within the brain while reducing systemic side effects, representing an advantageous alternative to conventional nanocarrier systems for GBM treatment. However, it is important to acknowledge that each carrier type presents unique challenges, including stability, off-target interactions, and variable clinical efficacy.
- Conclusion: Peptide-based nanocarriers constitute a versatile and promising class of delivery vehicles to overcome BBB-associated obstacles in glioblastoma therapy. To optimize their clinical utility, further efforts should focus on enhancing peptide stability in vivo, minimizing off-target effects, and improving targeting specificity. Rational design strategies and advanced engineering—including multifunctional and stimuli-responsive peptides—are expected to drive progress toward clinical translation. Such innovations hold substantial promise for improving therapeutic outcomes and may establish peptide-guided nanomedicine as a pivotal approach in targeted GBM therapy.
- Keywords: Glioblastoma, Blood-Brain Barrier, Peptide-Based Nanocarriers, Drug Delivery, Targeted Therapy
