siRNA based therapeutics have become the next frontier in molecular medicine. Though exosomes emerge as a promising drug delivery vehicle for siRNAs, significant hurdle remains in finding safe and effective loading methods. Traditional methods of loading exogenous siRNAs in exosomes are marked by certain limitations like siRNA aggregation, toxicity to the cells and their high experimental cost. As an electroporation and lipofection free approach, we show that the molecular conjugate of bovine lactoferrin with polyl-l-ysine electrostatically interacts with negatively charged siRNA, wherein lactoferrin as a ligand is captured by the GAPDH present in exosomes, loading siRNA in an effortless manner. This method exhibited transfection efficiency, colocalization percentage and colocalization threshold similar to electroporation. Furthermore, efficient uptake of exosomes loaded with siRNA via conjugate in recipient cells was observed. Our current study univocally establishes chemical free and non-mechanical method for the encapsulation and intercellular delivery of siRNA for wider therapeutic applications.

中文翻译：

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天然的配体-受体介导的siRNA在牛奶来源的外​​泌体中的负载。

基于siRNA的治疗剂已成为分子医学的下一个前沿领域。尽管外来体已成为siRNA的有希望的药物输送工具，但寻找安全有效的装载方法仍存在重大障碍。在外来体中装载外源siRNA的传统方法具有某些局限性，例如siRNA聚集，对细胞的毒性及其高昂的实验成本。作为无电穿孔和无脂转染的方法，我们证明了牛乳铁蛋白与聚-1-赖氨酸的分子共轭物与带负电的siRNA静电相互作用，其中乳铁蛋白作为配体被外泌体中存在的GAPDH捕获，以轻松方式加载siRNA 。该方法具有与电穿孔相似的转染效率，共定位百分比和共定位阈值。此外，观察到通过缀合物在受体细胞中有效吸收了装载有siRNA的外来体。我们当前的研究明确地建立了无化学和非机械方法用于siRNA的包封和细胞间递送，以用于更广泛的治疗应用。