Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, PR China.
Nanoscale. 2022 Mar 17;14(11):4098-4113. doi: 10.1039/d1nr08170e.
Gene therapy has been used in a variety of diseases and shows brilliant anticancer or cancer suppression effects. Gene therapy is gradually evolving as the most compelling frontier hotspot in the field of cancer therapy. The current vehicles used in gene therapy have poor safety and low delivery efficiency, and thus, it is urgent to develop novel delivery vehicles for gene therapy. Due to the excellent stability and biosafety of exosomes, their use as drug carriers for novel nucleic acid therapy is in full swing, revealing huge prospects for clinical application. Mesenchymal stem cells (MSCs) have a natural homing property and can spontaneously accumulate at injury sites, inflammation sites, and even tumour sites. This feature is attributed to a variety of tropism factors expressed on their surface; for example, CXC chemokine receptor type 4 (CXCR4) can specifically bind to the highly expressed stromal cell derived factor-1 (SDF-1) on the tumour surface, which is essential for accumulation of MSCs at the tumour site. The mesenchymal stem cells used in this study were genetically engineered to obtain exosomes with high CXCR4 expression as carriers for targeted gene-drug delivery, and then, the Survivin gene was loaded electrotransformation to construct a brand-new gene-drug delivery system (CXCR4 Exo/si-Survivin). Finally, related and experiments were conducted. We observed that the new delivery system can efficiently aggregate at the tumour site and release siRNA into tumour cells, knocking down the Survivin gene in tumour cells and thereby inhibiting tumour growth. This new gene-drug delivery system has tremendous clinical transformation value and provides a new strategy for clinical treatment of tumours.
基因治疗已被应用于多种疾病，并显示出出色的抗癌或抑癌效果。基因治疗作为癌症治疗领域最具吸引力的前沿热点，正在逐步发展。目前用于基因治疗的载体安全性差、递送效率低，因此，迫切需要开发新型基因治疗递送载体。由于外泌体具有优异的稳定性和生物安全性，它们作为新型核酸治疗的药物载体正在蓬勃发展，显示出巨大的临床应用前景。间充质干细胞（MSCs）具有天然的归巢特性，能够自发地聚集在损伤部位、炎症部位甚至肿瘤部位。这种特性归因于其表面表达的多种趋化因子受体；例如，CXC 趋化因子受体 4（CXCR4）可以特异性结合肿瘤表面高度表达的基质细胞衍生因子-1（SDF-1），这对于 MSCs 在肿瘤部位的聚集是必不可少的。本研究中使用的间充质干细胞经过基因工程改造，获得了高表达 CXCR4 的外泌体作为靶向基因药物递送的载体，然后通过电转化装载 Survivin 基因，构建了全新的基因药物递送系统（CXCR4 Exo/si-Survivin）。最后进行了相关实验。我们观察到，新的递送系统可以有效地聚集在肿瘤部位，并将 siRNA 释放到肿瘤细胞中，从而敲低肿瘤细胞中的 Survivin 基因，抑制肿瘤生长。这种新型基因药物递送系统具有巨大的临床转化价值，为肿瘤的临床治疗提供了新策略。
