Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China.
Medical College, Shaoguan University, Shaoguan, 512026, People's Republic of China.
Int J Nanomedicine. 2023 Oct 12;18:5733-5748. doi: 10.2147/IJN.S422416. eCollection 2023.
Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).
Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptotic activities of Qu-exosome-SPIONs/MF were evaluated both in vitro and in vivo.
The Qu-exosome-SPIONs were well constructed and harvested by magnetic separation with a uniform size and shape in a diameter of approximately 86.2 nm. The water solubility of quercetin increased 1.97-fold when loaded into the SPION-modified exosomes. The application of SPIONs/MF endowed the Qu-exosomes with favorable targeting capacity. In vitro studies showed that Qu-exosome-SPIONs/MF more effectively inhibited or attenuated β cell apoptosis and promoted insulin secretion in response to elevated glucose (GLC) compared with quercetin or Qu-exosome-SPIONs. In vivo studies demonstrated that Qu-exosome-SPIONs/MF displayed an ideal pancreatic islet targeting capacity, thereby leading to the restoration of islet function.
The Qu-exosome-SPIONs/MF nano-delivery system significantly enhanced the quercetin concentration in pancreatic islets and thereby improved pancreatic islet protection.
槲皮素对 2 型糖尿病（T2DM）胰岛功能的改善具有理想的治疗效果。然而，由于其生物利用度差和在胰岛中浓度有限，槲皮素的治疗益处受到阻碍。在这项研究中，制备了超顺磁性氧化铁纳米颗粒（SPION）修饰的外泌体来负载槲皮素，希望在外力（MF）的帮助下赋予槲皮素增强的水溶性和主动靶向能力。
通过利用 N-羟基琥珀酰亚胺（NHS）缀合化学合成转铁蛋白修饰的 SPION（Tf-SPION），并通过电穿孔获得负载槲皮素的外泌体（Qu-exosomes）。Tf-SPION 修饰的负载槲皮素的外泌体（Qu-exosome-SPIONs）是通过转铁蛋白（Tf）和转铁蛋白受体（TfR）的自组装产生的。通过高效液相色谱（HPLC）分析确定槲皮素的溶解度。体外和体内评估了 Qu-exosome-SPIONs/MF 的胰岛靶向能力和胰岛素分泌激动剂和抗凋亡活性。
Qu-exosome-SPIONs 构建良好，并通过磁性分离收获，粒径均匀，形状接近 86.2nm。当负载到 SPION 修饰的外泌体中时，槲皮素的水溶性增加了 1.97 倍。MF 的应用使 Qu-exosomes 具有良好的靶向能力。体外研究表明，与槲皮素或 Qu-exosome-SPIONs 相比，Qu-exosome-SPIONs/MF 更有效地抑制或减弱了高葡萄糖（GLC）刺激下β细胞凋亡并促进胰岛素分泌。体内研究表明，Qu-exosome-SPIONs/MF 显示出理想的胰岛靶向能力，从而恢复胰岛功能。
Qu-exosome-SPIONs/MF 纳米递药系统显著提高了胰岛中的槲皮素浓度，从而改善了胰岛保护。
