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

doi:10.7503/cjcu20240265

Abstract

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

CLC Number:

TrendMD:

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[J]. Chem. J. Chinese Universities, 2025, 46(1): 20240265.

Figures/Tables 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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