Recently, the team of Yueqing Gu and Siwen Li from the School of Engineering has published a series of research results on extracellular vesicles for the treatment of aging-related diseases in the prestigious journal Advanced Materials and the leading journal Nano Letters.
Alzheimer's disease (AD) is a common neurodegenerative disease, and there is a lack of effective therapeutic means to slow down or stop the progression of the disease. In recent years, neuroactivating optogenetic technologies have brought new hope for the treatment of various neurodegenerative diseases because of their ability to “reboot” degenerative neurons, promote neurotransmitter release, and accelerate synaptic remodeling. However, the clinical application of optogenetic technologies has been hindered by the problems of invasiveness and the difficulty of maintaining long-term therapeutic effects.
To address these bottlenecks, the team proposes a new strategy to utilize differentiated stem cells to generate functional materials to enhance the applicability of optogenetic therapy. Through the differentiation of induced pluripotent stem cells (iPSCs), stem cells (TenSCs) with “tentacle-like” morphology were obtained, from which TenSCev “tentacle” vesicles were isolated, which inherited the biological functions of the parental cells and have excellent neurotargeting properties. These vesicles inherited the biological functions of the parental cells, and have excellent neural targeting ability and repair potential in pathological environments. Based on this, the research team used TenSCev as a functional carrier to deliver optogenetic components, thus realizing truly non-invasive and controllable neuronal activation. At the same time, the abundant pathological environment repair substances in TenSCev also significantly improved the local neural environment, effectively halted the disease process, and enhanced the cognitive performance of AD model mice and aged rats.
Overall, the concept of “generating specific functional biomaterials from differentiated stem cells” proposed by the research group has reintroduced the potential of several neuromodulatory technologies in the treatment of neurological diseases, and has considerable translational potential. The related results, entitled “Noninvasive optogenetics realized by iPSC-derived tentacled carrier in Alzheimer's disease treatment”, were published in the prestigious journal Advanced Materials. Prof. Yueqing Gu and Prof. Si-Wen Li of the College of Engineering are the co-corresponding authors of this paper, Dr. Yuewen Zhai (Class of 2022) and Shihao Shi (Class of 2021) are the co-first authors of this paper, and China Pharmaceutical University (CPU) is the first corresponding author of this paper.
Mesenchymal stem cell exosomes show great potential for application in the field of anti-skin aging. However, how to enhance the transdermal effect of exosomes and how to effectively control the transdermal depth remains a great challenge. Exosomes need to be effectively delivered to the dermis in order to improve collagen regeneration, reduce wrinkles, sagging and other aging manifestations, and thus better exert anti-aging effects. Most of the existing exosome application methods rely on invasive means such as hydrafacial and microneedle injections, which are complex, technically demanding and may pose safety risks. Therefore, how to efficiently deliver exosomes to the dermis in a non-destructive way has become an urgent technical challenge.
The team developed a non-invasive, light-controlled, exosome transdermal system with strong tissue penetration capability. The nano-system takes exosome as the core and targets the matrix metalloproteinase 1 (MMP1) overexpressed siRNA in the dermis as the shell, forming an exosome spherical nucleic acid (ESNA) with a three-dimensional structure, which increases the tissue penetration ability, and further asymmetrically modifies the visible light-responsive gas-producing molecules on the surface of the ESNA to form an exosome-based spherical nucleic acid nano-motor (NM- (NM-ESNA), which generates a gas gradient as a driving force under light, giving NM-ESNA excellent light-controlled motility and transdermal properties. The results were published as “Light-controlled small extracellular vesicle-based spherical nucleic acid nanomotor for enhanced transdermal delivery The results were published in Nano Letters, a leading journal in the field, with Prof. Si-Wen Li from the College of Engineering as the corresponding author, Dr. Yu Li, a PhD student of Class 2021, as the first author, and China Pharmaceutical University (CPU) as the sole correspondent.
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