基因治疗作为当今流行的疗法之一，在各种疾病的治疗中取得了巨大的成功。然而，基因治疗的安全性、疗效和适用性也备受关注。微泡辅助超声引导下的基因治疗与传统方法相比具有以下优势：首先，这种策略能使治疗核酸有效地通过体内存在的天然屏障，如细胞膜屏障、血脑屏障、血视网膜屏障，可使药物富集在传统递送方法无法覆盖的病灶区域，进一步扩大了基因治疗的应用范围。其次，可以通过控制超声波的照射范围，将基因转染区域限制在病变区域，从而有效控制基因治疗脱靶的风险。此外，在超声成像和磁共振成像等多种成像技术的支持下，基因治疗过程可以在图像引导下进行，这将大大提高基因治疗的安全性。
近日，北京大学戴志飞教授、刘仁发副研究员和孙德胜副教授等人在Science China Materials发表综述论文，重点介绍了超声波增强基因递送策略的进展，关注该策略的相关机制、衍生技术和相关前沿应用，并对该基因递送策略的局限性和未来前景进行了讨论。
Figure 1. Schematic diagram of various UCAs for gene delivery and gene-load microbubbles. (a) Schematic illustration of classical UCAs—microbubbles with lipid shells and gaseous cores. (b–d) Schematic illustration of the unique UCAs reported in the scientific literature. (e, f) Schematic illustration of two gene-loaded microbubbles. Microbubbles non-covalently bind liposomes containing target genes via streptavidin affinity, or attract negatively charged nucleic acids via cationic materials.![]()
Figure 2. Schematic of the mechanisms involved in drug delivery by ultrasound combined with microbubbles. (a) Intercellular tight junction disruption by microbubble extrusion under cavitation. This process can facilitate gene to cross the barriers and reach deeper tissue. (b) Microbubbles in the inertial cavitation phase generate shock waves and microjets that punch holes in the cell surface. Under stable cavitation, mechanical forces generated by microbubbles oscillating rotate cell membrane phospholipids to generate hydrophilic pores. It is known as sonoporation. (c) Stimulation of the cell surface by the mechanical forces or ions in-flow due to sonoporation leads to enhanced cellular endocytosis.![]()
Figure 3. Schematic diagram of the relations between microbubble behaviors and ultrasonic parameters. The behavior of microbubbles is strongly dependent on the changes in ultrasound parameters, with stable cavitation occurring at low acoustic pressures and inertial cavitation at high acoustic pressures, which leads to the rupture of the microbubbles.Figure 4. Schematic diagram of microbubble-assisted ultrasound guided gene therapy related applications.Zhen Tie, Shuhao Zhang, Yunfeng Qu, Mengxuan Wang, Renfa Liu, Desheng Sun, Zhifei Dai. Advances in microbubble-assisted ultrasound-guided gene therapy: Mechanisms and applications. Sci. China Mater. (2024).https://doi.org/10.1007/s40843-024-2993-4
![]()
点击左下角“阅读原文”，阅读以上文章PDF原文
![]()
