College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2654-2663. doi: 10.1021/acsabm.0c01613. Epub 2021 Feb 18.
We describe the development of a neuropilin-1 binding peptide (RGERPPR)-ferritin nanocage that specifically targets tumor cells. Herein, the tumor-penetrating peptide RGERPPR motif was modified at the C-terminal of human H chain ferritin (HFtn) using flexible linker moieties. Since the C-terminal of HFtn is positioned toward the inner cavity, relatively long linkers (GGGGS) were used, in which the MMP-2 cleavage site was inserted in the linker. The RGERPPR motif was proved to be exposed outside the protein shell by the effective cleavage at the linker region by MMP-2. The loading of paclitaxel (PTX) and HFtn-mMMP2-RGE was prepared by using the low concentration of urea. studies demonstrated that HFtn-mMMP2-RGE-PTX nanoparticles exhibited better cytotoxicity and could specifically bind to and be taken up by human lung cancer cells A549 that highly express NRP-1 receptor. Better penetrability and growth inhibitory effect were also verified by the 3D tumor spheroid experiment. The results confirmed that the tumor-targeting and penetration peptide RGERPPR-modified ferritin had great potential in enhancing tumor therapy and could be a promising therapeutic agent.
我们描述了一种神经纤毛蛋白-1 结合肽（RGERPPR）-铁蛋白纳米笼的开发，该纳米笼专门针对肿瘤细胞。在此，使用柔性连接子修饰物在人 H 链铁蛋白（HFtn）的 C 末端修饰肿瘤穿透肽 RGERPPR 基序。由于 HFtn 的 C 末端位于内腔，因此使用相对较长的连接子（GGGGS），其中 MMP-2 切割位点插入连接子中。通过 MMP-2 在连接区域的有效切割，证明 RGERPPR 基序暴露在蛋白壳外。通过使用低浓度的脲制备紫杉醇（PTX）和 HFtn-mMMP2-RGE 的负载。研究表明，HFtn-mMMP2-RGE-PTX 纳米颗粒表现出更好的细胞毒性，并且可以特异性结合并被高表达 NRP-1 受体的人肺癌细胞 A549 摄取。通过 3D 肿瘤球体实验也验证了更好的穿透性和生长抑制作用。结果证实，靶向肿瘤和穿透肽 RGERPPR 修饰的铁蛋白在增强肿瘤治疗方面具有巨大潜力，可能成为一种有前途的治疗剂。
