纳米医学
丝素
伦瓦提尼
材料科学
肝细胞癌
生物利用度
药理学
纳米技术
癌症研究
纳米颗粒
丝绸
医学
复合材料
索拉非尼
作者
Kaxi Yu,Yu Wang,Hongxiang Sun,Yijie Lou,Hanxiao Bao,Xuanhao Wang,Jinguo Zhang,Junhui Shi,Guping Tang,Qiwen Wang,Hongzhen Bai
标识
DOI:10.1021/acsami.4c16424
摘要
Multitarget tyrosine kinase inhibitors (TKIs) serve as first-line therapeutics in the systemic treatment of hepatocellular carcinoma (HCC), yet their clinical effectiveness is hampered by suboptimal pharmacokinetics and bioavailability. There is a critical need to enhance the circulation, tumor targeting, and infiltration of TKIs. In this context, we developed a silk fibroin (SF)-based nanomedicine that exploits the chemical versatility and conformation tunability of SF. Folic acid (FA) with affinity toward HCC cells is utilized to functionalize SF, simultaneously aiding in the pH-sensitive β-sheet transitions of SF. This dynamic conformation behavior is key to improving the nanomedicine's circulation, biological adhesion, and tumor localization. By encapsulating Lenvatinib (Leva) TKI, the nanomedicine exhibits tumor-targeted accumulation and potent inhibition on HCC cell survival and angiogenesis, thereby amplifying Leva's bioavailability and therapeutic impact. Owing to SF's low immunogenicity and high reproducibility, this SF-based approach for TKI delivery holds substantial promise for advancing HCC systemic therapy.
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