Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood–brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.

中文翻译：

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蛋白质构象的调节使模拟病毒纳米颗粒能够细胞选择性靶向，用于胶质母细胞瘤的 siRNA 治疗

原位胶质母细胞瘤（GBM）具有侵袭性生长模式和复杂的发病机制，成为中枢神经系统（CNS）最常见和致命的肿瘤之一。 RNA疗法的出现为GBM的治疗带来了希望。然而，将 RNA 药物有效、精确地递送至具有高度细胞异质性的大脑中特定肿瘤细胞的研究仍在继续。在此，提出了一种通过脂质纳米环境调节蛋白质构象的策略，以定制设计具有优异选择性细胞靶向能力的模拟病毒纳米颗粒（VMN），从而高效、精确地递送小干扰RNA，从而有效治疗GBM。优化后的VMN不仅保留了像天然病毒一样穿过血脑屏障并通过溶酶体逃逸释放RNA的能力，而且确保了GBM区域的精确富集。这项研究为定制设计具有卓越细胞选择性靶向能力的 VMN 奠定了概念基础，并为 RNA 疗法有效治疗 GBM 和 CNS 肿瘤开辟了可能性。