骨桥蛋白
癌症研究
转移
肺癌
纳米-
癌症
医学
肿瘤科
内科学
工程类
化学工程
作者
Lei Zhou,Hongjun Zhuang,Qing Chen,Liping Jiang,Xuemin Han,Yizhi Ge,Tai-Wei Zhang,Haifeng Liang,Wang Ding,Ming Qi,Jian Dong,Tao Yi
标识
DOI:10.1016/j.cej.2021.132131
摘要
• TFA targeted NSCLC-SM and promoted chemosensitivity via disrupting OPN/αvβ3 interaction. • Thickness control and mass preparation of H-MnO 2 was achieved via reducing KMnO 4 by PEI. • TFA-modified, DDP-loaded MnO 2 nanocapsule H-MnO 2 /DDP(Cy)-TFA was fabricated. • H-MnO 2 /DDP(Cy)-TFA significantly suppressed progression of NSCLC-SM. Resistance to chemotherapy is a key factor affecting Non-small cell lung cancer spinal metastasis (NSCLC-SM) treatment efficiency. In this study, Osteopontin (OPN), an intracellular and a secreted glycoprotein, showed overexpression in NSCLC-SM. Further studies demonstrated that OPN promoted chemoresistance by activating mTORC2/AKT/NF-κB/MDR1 signaling via interaction with integrin αvβ3. Subsequently, it was confirmed that a specific inhibitor of OPN/αvβ3, the pentapeptide Gly-Arg-Gly-Asp-Ser (TFA), targeted NSCLC-SM and promoted chemosensitivity by competitively blocking the OPN/αvβ3 interaction and by inhibiting the downstream signaling. Therefore, a TFA-modified and cisplatin (DDP)-loaded hollow MnO 2 structure (H-MnO 2 /DDP(Cy)-TFA nanocapsules) was fabricated in the present study. The H-MnO 2 /DDP(Cy)-TFA targeted OPN, exhibited responses to the tumor microenvironment, and demonstrated high drug loading and controlled release. In a NSCLC-SM mouse model, H-MnO 2 /DDP(Cy)-TFA enhanced chemosensitivity and suppressed tumor progression via combination effect of targeted inhibition of OPN and controlled release of DDP. Collectively, the present study elucidated the mechanism underlying OPN-mediated NSCLC chemoresistance and a nano-drug delivery platform was developed as a new therapeutic strategy for precisely targeting NSCLC-SM and for enhancing chemosensitivity.
科研通智能强力驱动
Strongly Powered by AbleSci AI