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<p>Glioblastoma (GBM) remains uniformly lethal due to diffuse invasion, extensive molecular heterogeneity, and a profoundly immunosuppressive microenvironment. Nucleic-acid therapeutics—including antisense oligonucleotides, RNA interference, messenger RNA, and CRISPR-based genome editing—offer programmable control over oncogenic drivers and immune pathways, yet their clinical translation is hindered by rapid nuclease degradation, systemic clearance, restricted blood–brain-barrier transport, inefficient cellular uptake, and endosomal entrapment. Recent progress in nanotechnology has enabled the rational design of nanoparticle platforms that overcome these multilayered biological obstacles. This review summarizes advances (2022–2025) in lipid and biomimetic nanocarriers engineered to enhance nucleic-acid delivery for GBM therapy. For instance, ionizable lipid nanoparticles with pH-responsive chemistry and optimized head-group design achieve efficient cytosolic release with improved biocompatibility, while biomimetic systems, such as cell-membrane-, lipoprotein-, virus-, DNA-, and exosome-mimicking platforms, leverage natural transport and recognition pathways for tumor-specific targeting and immune evasion. Finally, we discuss translational considerations, including GMP-compatible manufacturing, batch consistency, long-term safety and immunogenicity, and advanced model selection, and outline future opportunities in high-throughput lipid discovery, AI-assisted ligand design, hydrogel-mediated spatiotemporal release, and patient-tailored nanotherapies. Collectively, these emerging nanocarriers offer a convergent strategy to navigate physiological barriers and advance precision nucleic-acid therapeutics against glioblastoma.</p>

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Recent advances in lipid and biomimetic nanocarriers for nucleic acid delivery in glioblastoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Chengyan Xu,
  • Zixia He,
  • Jiabin Li

摘要

Glioblastoma (GBM) remains uniformly lethal due to diffuse invasion, extensive molecular heterogeneity, and a profoundly immunosuppressive microenvironment. Nucleic-acid therapeutics—including antisense oligonucleotides, RNA interference, messenger RNA, and CRISPR-based genome editing—offer programmable control over oncogenic drivers and immune pathways, yet their clinical translation is hindered by rapid nuclease degradation, systemic clearance, restricted blood–brain-barrier transport, inefficient cellular uptake, and endosomal entrapment. Recent progress in nanotechnology has enabled the rational design of nanoparticle platforms that overcome these multilayered biological obstacles. This review summarizes advances (2022–2025) in lipid and biomimetic nanocarriers engineered to enhance nucleic-acid delivery for GBM therapy. For instance, ionizable lipid nanoparticles with pH-responsive chemistry and optimized head-group design achieve efficient cytosolic release with improved biocompatibility, while biomimetic systems, such as cell-membrane-, lipoprotein-, virus-, DNA-, and exosome-mimicking platforms, leverage natural transport and recognition pathways for tumor-specific targeting and immune evasion. Finally, we discuss translational considerations, including GMP-compatible manufacturing, batch consistency, long-term safety and immunogenicity, and advanced model selection, and outline future opportunities in high-throughput lipid discovery, AI-assisted ligand design, hydrogel-mediated spatiotemporal release, and patient-tailored nanotherapies. Collectively, these emerging nanocarriers offer a convergent strategy to navigate physiological barriers and advance precision nucleic-acid therapeutics against glioblastoma.