Light-Controlled Small Extracellular Vesicle-Based Spherical Nucleic Acid Nanomotor for Enhanced Transdermal Delivery against Skin Aging.

Yu Li, Lu Qian, Fei Liu, Shilong Xu, Lian Zhou, Chenxi Wei, Yanqin Zhang, Yuewen Zhai, Yueqing Gu, Siwen Li

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, Jiangsu Province, China.Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Jiangning District, Nanjing, 211198, Jiangsu Province, China. · pubmed

Paper

Abstract

Small extracellular vesicles (sEV) derived from mesenchymal stem cells hold promise for anti-skin aging, yet their clinical application is hindered by poor transdermal permeability. Herein, we report an innovative light-controlled sEV-based spherical nucleic acid nanomotor (NM-ESNA). This nanosystem was composed of an sEV core and an MMP1-targeting siRNA shell, forming a 3D penetrative nanostructure. In addition, asymmetrically modified light-responsive gas-generating molecules were integrated into the nanomotor, enabling efficient dermal delivery. The light-controlled and enhanced transdermal delivery guaranteed synergistic anti-skin aging therapy through sEV-mediated paracrine effects and gene therapy targeting MMP1 in the dermis. On the basis of this deep transdermal delivery technology and the synergistic therapy strategy, NM-ESNA demonstrated outstanding anti-skin aging effects in a mouse model. This biocompatible nanosystem (NM-ESNA) enabled light-controlled and deep transdermal delivery, establishing a therapeutic platform with significant potential for sEV-based noninvasive anti-skin aging therapy.

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Research summary

The paper claims that a light-controlled small extracellular vesicle-based nanomotor enhances transdermal delivery of anti-aging therapies. This research addresses a novel approach to improve skin aging treatment, focusing on mechanisms that could potentially mitigate aspects of aging rather than merely treating symptoms.

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