超声调控的细胞膜表面氧化还原反应促进纳米粒摄取和内涵体逃逸

doi:10.7503/cjcu20240265

高等学校化学学报 ›› 2025, Vol. 46 ›› Issue (1): 20240265.doi: 10.7503/cjcu20240265

超声调控的细胞膜表面氧化还原反应促进纳米粒摄取和内涵体逃逸

李瑶¹, 翟婉莹¹, 王征¹, 张葆鑫³(), 赵燕军¹()

^1.天津大学药物科学与技术学院, 天津市现代药物传递及功能高效化重点实验室, 天津 300072
^2.俄罗斯喀山国立医科大学, 喀山 420012
^3.内蒙古医科大学第二附属医院, 呼和浩特 010000

收稿日期:2024-05-31 出版日期:2025-01-10 发布日期:2024-07-01
通讯作者: 张葆鑫,赵燕军 E-mail:197218725@qq.com;zhaoyj@tju.edu.cn
作者简介:第一联系人：共同第一作者.
基金资助:
国家自然科学基金(22075198);内蒙古科技厅科技计划项目(2021GG0174);支持地方高校改革发展资金(学科建设)资助

Ultrasound-aided Cellular Uptake and Endosomal Escape of Nanoparticles via the Membrane Surface Redox Reaction

LI Yao¹, ZHAI Wanying¹, WANG Zheng¹, Petrov Alexey M.², ZHANG Baoxin³(), ZHAO Yanjun¹()

^1.Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency，School of Pharmaceutical Science & Technology，Tianjin University，Tianjin 300072，China
^2.Kazan State Medial University，Kazan RT 420012，Russia
^3.the Second Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010000，China

Received:2024-05-31 Online:2025-01-10 Published:2024-07-01
Contact: ZHANG Baoxin, ZHAO Yanjun E-mail:197218725@qq.com;zhaoyj@tju.edu.cn
Supported by:
the National Natural Science Foundation of China(22075198);the Inner Mongolia Commission of Science and Technology Department, China(2021GG0174);the Fund for the Reforming and Development of Local Colleges and Universities(Discipline Construction), China

1. ESM to 20240265.pdf(963KB)

摘要/Abstract

摘要：

细胞摄取和内涵体逃逸是纳米药物递送的两个关键屏障. 研究发现, 细胞外表面的硫醇可以通过巯基-二硫化物/二硒化物交换反应同时克服这两个屏障. 然而, 该策略增强纳米药物递送的能力有限. 为了解决上述问题, 本文采用机械力(超声)来提高硫醇-二硫化物/二硒化物交换反应的动力学, 进而提高药物递送效率. 研究结果为提高纳米药物递送效率提供了新方法.

关键词: 氧化还原反应, 细胞摄取, 内涵体逃逸, 纳米药物

Abstract:

Cellular uptake and endosomal escape are two critical biological barriers to nanoscale drug delivery. The exofacial thiols at cell surface have been previously reported to simultaneously overcome these two barriers via the thiol-disulfide/diselenide exchange reaction. However， the power of such approach for nanomedicine delivery enhancement was limited. To address the above issue， we employed the mechanical force（ultrasound） that could significantly enhance the kinetics of thiol-disulfide/diselenide exchange reactions， and then the delivery efficiency. The discovery in the current work opens new avenues of tailored nanomedicine design to circumvent the delivery hurdles.

Key words: Redox reaction, Cellular uptake, Endosomal escape, Nanomedicine

中图分类号:

TrendMD:

李瑶, 翟婉莹, 王征, 张葆鑫, 赵燕军. 超声调控的细胞膜表面氧化还原反应促进纳米粒摄取和内涵体逃逸. 高等学校化学学报, 2025, 46(1): 20240265.

LI Yao, ZHAI Wanying, WANG Zheng, Petrov Alexey M., ZHANG Baoxin, ZHAO Yanjun. Ultrasound-aided Cellular Uptake and Endosomal Escape of Nanoparticles via the Membrane Surface Redox Reaction. Chem. J. Chinese Universities, 2025, 46(1): 20240265.

图/表 5

Fig.1 Physicochemical assessment of three type of micelles made of D⁃α⁃tocopheryl polyethylene glycol succinate(TPGS) derivatives（A） TPGS was conjugated with bifunctional molecule containing a disulfide or diselenide moiety. The disulfide/diselenide-free molecule was used as the control；（B） particle size analysis of three types of micelles with or without the fluorescent cargo（FITC）；（C） the surface charge of different types of micelles；（D） the loading of FITC in micelles. Data are presented as mean±standard deviation（n=3）.

Fig.2 Endocytosis pathway of three type of micelles in HeLa cells

Fig.3 Quantification of ultrasound⁃aided uptake of micelles surface⁃engineered with disulfide/diselenide in HeLa cellsa. FITC-CM； b. FITC-CM+US； c. FITC-SM； d. FITC-SM+US； e. FITC-SeM； f. FITC-SeM+US. The effect of ultrasound（US） on the cellular uptake of three types of micelles. US condition： 1 MHz， 1.0 W/cm2， 20% duty cycle， 120 s. n.s. indicates no significant difference， * p<0.05， ** p<0.01， *** p<0.001（n=3）.

Fig.4 Assessment of endosomal escape of three type of micelles in HeLa cells at the presence or absence of ultrasound(US)(n=3)

Fig.5 Pearson’s correlation coefficients reflect endosomal escape capacity of three type of micelles in HeLa cells at the presence or absence of ultrasound(US)a. FITC-CM； b. FITC-CM+US； c. FITC-SM； d. FITC-SM+US； e. FITC-SeM； f. FITC-SeM+US. Plot of Pearson’s correlation coefficient between FITC-labelled micelles and endosomes/ lysosomes indicated by the Lyso Tracker. US condition： 1 MHz， 1.0 W/cm2， 20% duty cycle， 120 s. n.s. indicates no significant difference， * p<0.05， ** p<0.01， *** p<0.001（n=3）.

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超声调控的细胞膜表面氧化还原反应促进纳米粒摄取和内涵体逃逸

Ultrasound-aided Cellular Uptake and Endosomal Escape of Nanoparticles via the Membrane Surface Redox Reaction

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