Liu Songyang, Yi Dan, Ma Rui, Zhang Wei
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130061, People's Republic of China.
Department of VascularSurgery Qiqihar first hospital, Qiqihar City, Heilongjiang Province, 161000, People's Republic of China.
Int J Nanomedicine. 2025 Mar 29;20:3933-3944. doi: 10.2147/IJN.S489777. eCollection 2025.
Sorafenib (SF) is a small molecule involved in tumor proliferation and angiogenesis. SF is inhibitor of several kinases, including RAF, VEGFR, and PDGFR. However the weak targeting ability of SF for liver tumor tissues is the major problem in clinical therapy. Therefore, a SF-loaded folic acid-targeted liposome drug delivery system was devised for targeting liver tumor therapy in this study.
Folic acid (FA), HSPC, DSPE-PEG, CHO, and SF were composed to prepare a folic acid-targeted SF-loaded liposome (LSF) drug delivery system. LSF and drug loading content was established through thin-film-hydration technique and HPLC, respectively. The particle size and stability of LSF were examined by dynamic light scattering (DLS). The inhibition effect of LSF was elucidated in vitro on liver cancer cells through cell cytotoxicity and apoptosis experiments. The tumor-inhibiting efficacy was measured on liver xenograft model.
The drug loading content (DLC) of LSF was 3.6%. The diameter of LSF was 197.1±16.6 nm, and LSF was stable during 24 h. Liver cancer cells could be effectively inhibited by LSF in vitro. LSF could substantially induce apoptosis. Also, LSF could inhibit tumor growth effectively in vivo. LSF could reduce side effects of SF demonstrated by bio-safety tests.
LSF is a FA-targeted drug delivery system that could effectively inhibit the progression of liver cancer.
索拉非尼（SF）是一种参与肿瘤增殖和血管生成的小分子。SF是几种激酶的抑制剂，包括RAF、VEGFR和PDGFR。然而，SF对肝肿瘤组织的靶向能力较弱是临床治疗中的主要问题。因此，本研究设计了一种载有SF的叶酸靶向脂质体药物递送系统用于靶向肝肿瘤治疗。
将叶酸（FA）、氢化大豆卵磷脂（HSPC）、二硬脂酰磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）、胆固醇（CHO）和SF组成，制备叶酸靶向载SF脂质体（LSF）药物递送系统。分别通过薄膜水化技术和高效液相色谱法确定LSF和药物负载量。通过动态光散射（DLS）检测LSF的粒径和稳定性。通过细胞毒性和凋亡实验在体外阐明LSF对肝癌细胞的抑制作用。在肝异种移植模型上测定肿瘤抑制效果。
LSF的药物负载量（DLC）为3.6%。LSF的直径为197.1±16.6nm，且在24小时内稳定。LSF在体外可有效抑制肝癌细胞。LSF可显著诱导凋亡。此外，LSF在体内可有效抑制肿瘤生长。生物安全性测试表明LSF可降低SF的副作用。
LSF是一种叶酸靶向药物递送系统，可有效抑制肝癌进展。
