时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31
研究问题
Accordingly, RPM-based therapies are under clinical evaluation across multiple indications, including cancer, amyotrophic lateral sclerosis, fibrogenesis, and neurocutaneous syndromes., Despite these advantages, the clinical translation of RPM for PD remains limited by systemic toxicity under high-dose or long-term administration and by the restrictive blood-brain barrier (BBB), which severely constrains drug delivery to the central nervous system (CNS)., Although nanotechnology, exemplified by clinically evaluated albumin-bound rapamycin (nab-rapamycin, ABI-009), has been explored to improve rapamycin pharmacokinetics and reduce systemic toxicity (), effective CNS delivery remains limited, as most nano-formulations exhibit poor brain accumulation after systemic administration.
方法
Male C57BL/6 mice (8–10 weeks) were purchased from the Experimental Animal Center of Xi’an Jiaotong University School of Medicine.;All animal procedures were approved by the Biomedical Ethics Committee of Health Science Center of Xi’an Jiaotong University (XJTUAE2025-3840) and conducted in accordance with the corresponding institutional guidelines and the AVMA Guidelines for the Euthanasia of Animals.;Blood samples were obtained from C57BL/6 mice via orbital venous plexus puncture.;The collected blood underwent sequential centrifugation (3000 × g, 10 min; 12,000 × g, 40 min at 4 °C), followed by filtration through 0.22 µm membranes to remove cell debris and large particles.
核心结论
Transmission electron microscopy (TEM) images revealed that the isolated EXO exhibited a predominantly spherical or near-spherical vesicular morphology ().;These findings raise the possibility of transferrin–TfR interactions between blood-derived EXO and BBB endothelial cells, which may facilitate the delivery of blood-derived exosomes to the brain ( and ).;TEM and NTA showed that EXO-RPM retained a predominantly spherical or near-spherical vesicular morphology similar to that of blank exosomes, with a slight size increase to about 140 nm, good dispersity, and a modest rise in zeta potential, indicating successful RPM loading (). ‖ 结论:Collectively, our findings demonstrate the therapeutic potential of coordinated BBB modulation and exosome-mediated autophagy regulation and support further preclinical evaluation of EXO-RPM combined with FUS as a potential treatment strategy for PD.
局限
Moreover, we cannot exclude the possibility that the observed therapeutic effects may also be partially associated with previously reported neuroprotective properties of exosomes and focused ultrasound.
对本项目的价值
★☆☆☆☆ 脑老化是最大未满足需求,也是终点最难量化的领域;biomarker 与认知读数选择最敏感。
全文来源
PMC JATS 全文(正文 48,674 字符,已过标题/DOI 逐字归属校验)
原文题录
- 英文标题:Ultrasound-Guided Mobilization of Dual Autophagic Cleaning Crew by Exosomal Rapamycin Ameliorates the Progression of Parkinsonism.
- 期刊与标识:Int J Nanomedicine · PMID 42953137 · DOI 10.2147/ijn.s625730
B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)
本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。
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