Xu Wentao, Zheng Jiajia, Zhang Jiaqi, Shi Houhui, Peng Weili, Liu Yang, Feng Guodong, Wang Yuguang, Liang Yi-Jun, Chen Jun
Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, People's Republic of China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, People's Republic of China.
Int J Nanomedicine. 2025 Mar 27;20:3845-3860. doi: 10.2147/IJN.S509387. eCollection 2025.
Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes.
cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model.
The prepared nanocomplex exhibits a surface charge of -9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice.
Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.
肝癌是全球最常见的癌症之一，约90%的原发性肝癌为肝细胞癌（HCC）。然而，目前的全身治疗方案（无论是单药治疗还是联合治疗）都很有限，仅能带来适度的生存获益。药物的有效性在很大程度上取决于其在靶部位的浓度。因此，有效的药物递送系统必须增强药物在靶部位的蓄积，实现药物在该部位的选择性释放，并促进其从溶酶体中逃逸。
通过酰胺反应将c(RGDyK)修饰到载有二氢卟吩e6（Ce6）和阿霉素（DOX）的脂质体表面，制备cRGD-Lipo@Ce6/DOX。采用流式细胞术分析cRGD-Lipo@Ce6/DOX对HCC的靶向能力和摄取机制。为了研究超声刺激后的药物释放机制和亚细胞分布变化，进行了进一步研究。然后在HCC皮下荷瘤小鼠模型中评估这种双模态疗法的治疗效果和生物安全性。
制备的纳米复合物表面电荷为-9.91±2.94 mV，表观尺寸为118.07±1.46 nm。在载药脂质体表面修饰RGD环肽可增强对HCC的靶向和渗透效率。关于药物摄取机制和释放的体外实验表明，声动力疗法（SDT）产生的活性氧（ROS）促进药物从载体有效释放到非溶酶体区域。SDT与化疗联合治疗在HCC皮下荷瘤小鼠中实现了94%的肿瘤抑制率，并显示出优异的生物安全性。
因此，利用SDT联合化疗的联合治疗策略的有效性为HCC患者提供了额外的治疗选择。
