Abstract：
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.
摘要：
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的治疗提供了希望。然而,将RNA药物有效和精确地递送至具有高细胞异质性的大脑中的特定肿瘤细胞仍在进行中。这里,我们提出了一种通过脂质纳米环境（RPCLN）调节蛋白质构象的策略，以定制设计具有出色选择性细胞靶向能力的病毒模拟纳米颗粒（VMNs），导致有效和精确的小干扰RNA（siRNA）的有效治疗GBM。优化的VMN不仅保留了穿过血脑屏障（BBB）的能力，并像天然病毒一样通过溶酶体逃逸释放RNA，而且还确保了GBM区域的精确富集。这项研究为定制设计具有优越的细胞选择性靶向能力的VMN奠定了概念基础，并为有效治疗GBM和CNS肿瘤开辟了RNA疗法的可能性。本文受版权保护。保留所有权利。
