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形状自适应液体栓塞剂,用于超快和持久的血管栓塞。

Shape Self-Adaptive Liquid Embolic Agent for Ultrafast and Durable Vascular Embolization.

机构信息

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China.

Institute of Medical Health, Harbin Institute of Technology Zhengzhou Research Institute, Zhengzhou 450000, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2024 Jun 26;16(25):31936-31949. doi: 10.1021/acsami.4c02892. Epub 2024 Jun 13.

Abstract

Minimally invasive embolization greatly decreases the mortality resulting from vascular injuries while still suffering from a high risk of recanalization and systematic thrombosis due to the intrinsic hydrophobicity and poor adhesion of the clinically used liquid embolic agent of Lipiodol. In this study, a shape self-adaptive liquid embolic agent was developed by mixing biocompatible poly(acrylic acid) (PAA), two-dimensional magnesium-aluminum layered double hydroxide (LDH), and poly(ethylene glycol)200 (PEG200). Upon contact with blood, the injectable PAA-LDH@PEG200 would quickly absorb water to form an adhesive and mechanically strong PAA-LDH thin hydrogel within 5 s, which could firmly adhere to the blood vessel wall for ultrafast and durable embolization. In addition, benefiting from the "positively charged nucleic center effect" of LDH nanosheets, the liquid PAA-LDH@PEG200 could avoid vascular distension by PAA overexpansion and possess high shock-resistant mechanical strength from the blood flow. Furthermore, both in vitro and in vivo embolization experiments demonstrated the complete embolic capacity of liquid PAA-LDH@PEG200 without the occurrence of recanalization for 28 days and also the great potential to act as a platform to couple with chemotherapeutic drugs for the minimized transcatheter arterial chemoembolization (TACE) treatment of VX2 tumors without recurrence for 18 days. Thus, liquid PAA-LDH@PEG200 developed here possesses great potential to act as a shape self-adaptive liquid embolic agent for ultrafast and durable vascular embolization.

摘要

微创栓塞极大地降低了血管损伤导致的死亡率,但由于临床使用的液体栓塞剂 Lipiodol 固有疏水性和较差的粘附性,仍存在再通和系统血栓形成的高风险。在这项研究中,通过混合生物相容性的聚丙烯酸(PAA)、二维镁铝层状双氢氧化物(LDH)和聚乙二醇 200(PEG200),开发了一种形状自适应的液体栓塞剂。与血液接触后,可注射的 PAA-LDH@PEG200 会在 5 秒内迅速吸水,形成具有粘附性和机械强度的 PAA-LDH 薄水凝胶,可牢固地粘附在血管壁上,实现超快和持久的栓塞。此外,得益于 LDH 纳米片的“带正电荷的核酸中心效应”,液体 PAA-LDH@PEG200 可以避免 PAA 过度膨胀引起的血管扩张,并具有来自血流的高抗冲击机械强度。此外,体内外栓塞实验表明,液体 PAA-LDH@PEG200 具有完全的栓塞能力,28 天内无再通发生,并且具有作为平台与化疗药物结合的巨大潜力,用于最小化经导管动脉化疗栓塞(TACE)治疗 VX2 肿瘤,18 天内无复发。因此,这里开发的液体 PAA-LDH@PEG200 具有作为形状自适应液体栓塞剂实现超快和持久血管栓塞的巨大潜力。

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