Hong Min, Liu Xiaoyan, Ji Qinghong, Ou Mengyao, Yue Qiaoli, Cheng Shuang
School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, 252059, China.
School of Agricultural Science and Engineering, Liaocheng University, Liaocheng, 252059, China.
Drug Deliv Transl Res. 2025 Jan 3. doi: 10.1007/s13346-024-01783-8.
Erastin, as an effective ferroptosis inducer, has received extensive attention in anti-tumor research. To develop an oral nanocarrier for high efficient loading hydrophobic erastin, here we prepared a fluoro-liposome (FA-3 F-LS) by the self-assembly of the folic acid modified fluorinated amphiphiles-FA-3 F conjugates. The hydrophobic component of three perfluorooctyl chains endows the FA-3 F-LSs with high stability to resist the harsh gastrointestinal tract condition. Folic acids conjugated on the surface of FA-3 F-LSs ensure the better tumor targeting and higher oral bioavailability (32.1%) of erastin-loaded FA-3 F-LSs (erastin@FA-3 F-LSs) than free erastin (8.98%). As targeted anti-tumor nanomedicines, erastin@FA-3 F-LSs effectively inhibited the tumor cell proliferation in vitro by inducing ferroptosis through enhancing the glutathione (GSH) depletion, lipid peroxidation and generation of reactive oxygen species. In vivo studies demonstrated that FA-3 F-LSs displayed excellent application potential as a tumor-targeted oral drug delivery nanocarrier to depress the tumor growth with the loaded chemotherapeutic agents.
埃拉司亭作为一种有效的铁死亡诱导剂，在抗肿瘤研究中受到了广泛关注。为了开发一种用于高效负载疏水性埃拉司亭的口服纳米载体，我们通过叶酸修饰的氟化两亲物-FA-3F共轭物的自组装制备了一种氟脂质体（FA-3F-LS）。三个全氟辛基链的疏水成分赋予FA-3F-LS高稳定性，以抵抗恶劣的胃肠道环境。FA-3F-LS表面偶联的叶酸确保了负载埃拉司亭的FA-3F-LS（埃拉司亭@FA-3F-LS）比游离埃拉司亭（8.98%）具有更好的肿瘤靶向性和更高的口服生物利用度（32.1%）。作为靶向抗肿瘤纳米药物，埃拉司亭@FA-3F-LS通过增强谷胱甘肽（GSH）消耗、脂质过氧化和活性氧的产生诱导铁死亡，从而在体外有效抑制肿瘤细胞增殖。体内研究表明，FA-3F-LS作为一种肿瘤靶向口服给药纳米载体，在负载化疗药物时具有优异的应用潜力，可抑制肿瘤生长。
