Reprogramming Glioma-Associated Macrophages by Peptide-Drug Conjugates: A Novel Strategy to Sensitize Chemotherapy-Immunotherapy
Abstract：Glioblastoma (GBM) is the most common and aggressive primary malignant tumor in the central nervous system. The median survival time from initial diagnosis to death is approximately 15 months, with a 5-year survival rate of less than 10% [1]. GBM treatment has long been limited by low blood-brain barrier penetration and an immunosuppressive tumor microenvironment (TME). Glioma-associated macrophages (GAM), as a major component of TME, promote immune evasion and chemoresistance through M2 phenotype (M2-GAM) by disrupting antigen presentation and secreting anti-inflammatory cytokines, becoming a key factor in treatment failure [2]. In recent years, peptide-drug conjugates (PDC) have become a popular tool for overcoming the blood-brain barrier and modulating TME, due to their modular design and microenvironment-responsive properties. Li et al. [3] recently reported a novel PDC system (MAPDC), which successfully reprogrammed GAM from M2 to M1 phenotype by targeting the LRP1 receptor and achieving dual-responsive drug release, significantly enhancing the synergistic effect of chemotherapy-immunotherapy. This study not only reveals the potential of PDC in brain-targeted delivery but also provides a new paradigm for overcoming GBM resistance.
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Publication Date：2025-02-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：1( 124 )