Wang Ting, Li Zhimin, Lei Jiawei, Zhang Yuchen, Tong Yingpeng, Guan Xingang, Wang Shuangshuang
Department of Cardiology, The First People's Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), School of Medicine, Taizhou University, Taizhou 317500, PR China.
College of Medical Technology, Beihua University, Jilin 132013, PR China.
Int J Pharm X. 2025 Feb 26;9:100326. doi: 10.1016/j.ijpx.2025.100326. eCollection 2025 Jun.
Doxorubicin (Dox)-induced cardiotoxicity presents a significant challenge to fully harnessing its chemotherapeutic potential. Crocetin (Cro), a dicarboxylic acid found in the crocus flower and gardenia fruit, has shown remarkable antioxidant and anti-inflammatory activities. However, its poor aqueous solubility and limited cellular uptake severely constrain its further application in treating diseases. In this study, we developed Arg-Gly-Asp (RGD) peptide-decorated nanomicelles delivering Cro to alleviate Dox-induced cardiac injury. The RGD@M(Cro) nanomicelles exhibited excellent aqueous solubility and a drug-loading efficiency of 93.3 %. RGD-decorated micelles could enhance the cellular uptake of Cro in cardiomyocytes and inhibit approximately 60 % of HL-1 cell apoptosis through efficient reactive oxygen species (ROS) scavenging. In a cardiomyopathy mouse model, RGD@M(Cro) substantially reduced cardiac damage and improved cardiac indicators. This study highlights the great potential of RGD-decorated micelles in treating cardiac injury and other diseases.
阿霉素（Dox）诱导的心脏毒性对充分发挥其化疗潜力构成了重大挑战。藏红花素（Cro）是一种存在于藏红花花和栀子果实中的二羧酸，已显示出显著的抗氧化和抗炎活性。然而，其较差的水溶性和有限的细胞摄取严重限制了其在疾病治疗中的进一步应用。在本研究中，我们开发了用精氨酸-甘氨酸-天冬氨酸（RGD）肽修饰的纳米胶束来递送藏红花素，以减轻阿霉素诱导的心脏损伤。RGD@M（Cro）纳米胶束表现出优异的水溶性和93.3%的载药效率。RGD修饰的胶束可以增强藏红花素在心肌细胞中的细胞摄取，并通过有效清除活性氧（ROS）抑制约60%的HL-1细胞凋亡。在心肌病小鼠模型中，RGD@M（Cro）显著减轻了心脏损伤并改善了心脏指标。这项研究突出了RGD修饰胶束在治疗心脏损伤和其他疾病方面的巨大潜力。
