Ma Yin-Chu, Tang Xin-Feng, Xu You-Cui, Jiang Wei, Xin Yong-Jie, Zhao Wei, He Xu, Lu Li-Gong, Zhan Mei-Xiao
Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, China.
School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Biomater Sci. 2021 May 4;9(9):3401-3409. doi: 10.1039/d1bm00157d.
The combination of chemotherapy and radiotherapy (chemoradiotherapy) is a promising strategy, extensively studied and applied clinically. Meanwhile, radiosensitizers play an important role in improving clinical radiotherapy therapeutic efficacy. There are still some disadvantages in practical applications, because radiosensitizers and drugs are difficult to deliver spatio-temporally to tumor sites and work simultaneously with low efficiency for DNA damage and repair inhibition, leading to an inferior synergistic effect. Herein, a suitable radiosensitizer of nano-enabled coordination platform (NP@PVP) with bismuth nitrate and cisplatin prodrug is developed by a simple synthetic route to improve the effectiveness of chemo-radiation synergistic therapy. When NP@PVP is internalized by a tumor cell, the bismuth in NP@PVP can sensitize radiation therapy (RT) by increasing the amount of reactive oxygen species generation to enhance DNA damage after X-ray radiation; meanwhile, the cisplatin in NP@PVP can inhibit DNA damage repair with spatio-temporal synchronization. NP@PVP is demonstrated to exhibit higher sensitization enhancement ratio (SER) of 2.29 and excellent tumor ablation capability upon irradiation in vivo in comparison with cisplatin (SER of 1.78). Our strategy demonstrates that the RT sensitization effect of bismuth and cisplatin based NP@PVP has great anticancer potential in chemo-radiation synergistic therapy, which is promising for clinical application.
化疗与放疗相结合（放化疗）是一种很有前景的策略，已在临床上得到广泛研究和应用。同时，放射增敏剂在提高临床放射治疗疗效方面发挥着重要作用。然而在实际应用中仍存在一些缺点，因为放射增敏剂和药物难以在时空上输送到肿瘤部位，并且在抑制DNA损伤和修复方面效率低下，导致协同效应较差。在此，通过一种简单的合成路线开发了一种合适的纳米配位平台放射增敏剂（NP@PVP），该增敏剂含有硝酸铋和顺铂前药，以提高放化疗协同治疗的效果。当NP@PVP被肿瘤细胞内化时，NP@PVP中的铋可通过增加活性氧的生成量来使放射治疗（RT）增敏，从而增强X射线辐射后的DNA损伤；同时，NP@PVP中的顺铂可以在时空同步的情况下抑制DNA损伤修复。与顺铂（增敏增强比为1.78）相比，NP@PVP在体内照射时表现出更高的增敏增强比（SER），为2.29，并且具有出色的肿瘤消融能力。我们的策略表明，基于铋和顺铂的NP@PVP的放射增敏作用在放化疗协同治疗中具有巨大的抗癌潜力，有望应用于临床。
