UASSIGNED:血脑屏障(BBB)是将药物输送到大脑中的关键障碍。因此,开发先进的纳米药物递送平台来解决这一问题至关重要。我们先前筛选了具有15个氨基酸的小型狂犬病病毒糖蛋白15(RVG15)肽,并观察到大多数RVG15修饰的纳米颗粒在给药后1小时内进入大脑。高BBB穿透性使RVG15具有脑靶向药物递送系统的巨大潜力。此外,具有高载药量的多功能集成纳米平台,可调功能,控制药物释放对肿瘤治疗至关重要。沸石咪唑酯骨架(ZIF-8)是一种有前途的纳米药物递送系统。
未经评估:受仿生概念的启发,我们设计了RVG15包被的仿生ZIF-8纳米颗粒(RVG15-PEG@DTX@ZIF-8)用于多西他赛(DTX)递送,以实现小鼠胶质母细胞瘤的有效消除。这种仿生纳米治疗系统是通过一锅封装制备的,然后用RVG15-PEG缀合物涂覆。大小,形态学,稳定性,载药量,对RVG15-PEG@DTX@ZIF-8的释放进行了彻底研究。此外,我们进行了体外评估,细胞摄取能力,BBB渗透,和抗迁徙能力。我们还在小鼠模式下对这种仿生纳米治疗系统的生物分布和抗神经胶质瘤功效进行了体内评估。
未经评估:体外研究表明,这种仿生纳米治疗系统在HBMECs和C6细胞中具有优异的靶向效率和安全性,并且在穿越BBB方面具有很高的效率。此外,纳米粒子会导致大脑中DTX的快速积累,允许更深地渗透到神经胶质瘤肿瘤中。体内抗肿瘤实验结果表明,RVG15-PEG@DTX@ZIF-8对胶质瘤的生长和转移有明显的抑制作用,从而提高荷瘤小鼠的存活率。
UNASSIGNED:我们的研究表明,我们使用RVG15肽的仿生纳米治疗系统是穿越BBB和治疗胶质母细胞瘤的有前途且强大的工具。
UNASSIGNED: The blood-brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG15) peptide with 15 amino acids and observed that most of the RVG15-modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system.
UNASSIGNED: Inspired by the biomimetic concept, we designed RVG15-coated biomimetic ZIF-8 nanoparticles (RVG15-PEG@DTX@ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG15-PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG15-PEG@DTX@ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode.
UNASSIGNED: In vitro studies showed that, this bionic nanotherapeutic system exhibited excellent targeting efficiency and safety in HBMECs and C6 cells and high efficiency in crossing the BBB. Furthermore, the nanoparticles cause rapid DTX accumulation in the brain, allowing deeper penetration into glioma tumors. In vivo antitumor assay results indicated that RVG15-PEG@DTX@ZIF-8 significantly inhibited glioma growth and metastasis, thereby improving the survival of tumor-bearing mice.
UNASSIGNED: Our study demonstrates that our bionic nanotherapeutic system using RVG15 peptides is a promising and powerful tool for crossing the BBB and treating glioblastoma.