Zhang Man, Lin Jinti, Jin Jiakang, Yu Wei, Qi Yiying, Tao Huimin
Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, China.
Front Pharmacol. 2021 Dec 20;12:799588. doi: 10.3389/fphar.2021.799588. eCollection 2021.
Gold nanorods (GNRs) are intensively explored for the application in cancer therapy, which has motivated the development of photothermal therapy (PTT) multifunctional nanoplatforms based on GNRs to cure osteosarcoma (OS). However, the major limitations include the toxicity of surface protectants of GNRs, unsatisfactory targeting therapy, and the resistant effects of photothermal-induced autophagy, so the risk of relapse and metastasis of OS increase. In the present study, the GNR multifunctional nanoplatforms were designed and synthesized to deliver transcription factor EB (TFEB)-siRNA-targeting autophagy; then, the resistance of autophagy to PTT and the pH-sensitive cell-penetrating membrane peptide (CPP) was weakened, which could improve the tumor-targeting ability of the GNR nanoplatforms and realize an efficient synergistic effect for tumor treatment. Meanwhile, it is worth noting that the GNR nanoplatform groups have anti-lung metastasis of OS. This study provides a new reference to improve the efficacy of OS clinically.
金纳米棒（GNRs）在癌症治疗中的应用受到广泛探索，这推动了基于GNRs的光热疗法（PTT）多功能纳米平台的发展，以治疗骨肉瘤（OS）。然而，主要局限性包括GNRs表面保护剂的毒性、靶向治疗效果不理想以及光热诱导自噬的抵抗作用，因此骨肉瘤复发和转移的风险增加。在本研究中，设计并合成了GNR多功能纳米平台，以递送靶向自噬的转录因子EB（TFEB）-小干扰RNA；然后，自噬对PTT和pH敏感的细胞穿透膜肽（CPP）的抗性被削弱，这可以提高GNR纳米平台的肿瘤靶向能力，并实现肿瘤治疗的高效协同效应。同时，值得注意的是，GNR纳米平台组具有抗骨肉瘤肺转移的作用。本研究为临床上提高骨肉瘤的疗效提供了新的参考。
