Zheng Zhiyu, Williams Gareth R, Guo Honghua, Zheng Yilu, Xiu Mengting, Zhang Yanyan, Zhang Huan, Wang Kai, Xia Jindong, Wang Yu, Zhu Li-Min
College of Biological Science and Medical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, People's Republic of China.
UCL School of Pharmacy, University College London, London, UK.
Int J Nanomedicine. 2025 Apr 29;20:5593-5610. doi: 10.2147/IJN.S511891. eCollection 2025.
Owing to the limitations of single-mode cancer treatments, combination therapies have attracted much attention. However, constructing a platform for combination therapies in a simple and effective way and improving the overall treatment effect remains a challenge. Our aim was to combine sonodynamic therapy, radiotherapy and chemotherapy together and improve therapeutic outcomes within one nanoplatform.
In this work, we sought to exploit the properties of nanoscale heterojunctions to this end. A multifunctional BiO-TiO@polydopamine-doxorubicin (BTPD) nanoparticle platform was constructed as an anti-cancer theranostic. Under ultrasound irradiation, the BiO-TiO core can generate singlet oxygen to damage tumor cells. Meanwhile, the high-Z BiO can attenuate the energy of X-rays and scatter secondary electrons to enhance radiation damage in the tumor. A thin coating of polydopamine (PDA) increases the biocompatibility but also gives the particles the ability for photoacoustic imaging. Doxorubicin, a DNA repair inhibitor which can hinder tumor recovery from radiation damage, was loaded onto the PDA.
A comprehensive series of in vitro and in vivo assays demonstrated that the nanoparticles were effectively taken up into cancer cells, where they could induce ROS production and cause cell death. In vivo, this led to a marked reduction in tumor volume in a murine 4T1 cancer model.
The formulations developed here have significant potential for future investigation and exploration in the treatment of cancer.
由于单一模式癌症治疗方法存在局限性,联合疗法备受关注。然而,以简单有效的方式构建联合治疗平台并提高整体治疗效果仍然是一项挑战。我们的目标是将声动力疗法、放射疗法和化学疗法结合在一起,并在一个纳米平台内提高治疗效果。
在这项工作中,我们试图为此利用纳米级异质结的特性。构建了一种多功能BiO-TiO@聚多巴胺-阿霉素(BTPD)纳米颗粒平台作为抗癌诊疗剂。在超声照射下,BiO-TiO核可产生活性单线态氧以损伤肿瘤细胞。同时,高原子序数的BiO可衰减X射线的能量并散射二次电子,以增强肿瘤中的辐射损伤。聚多巴胺(PDA)薄涂层增加了生物相容性,还赋予颗粒光声成像能力。阿霉素是一种DNA修复抑制剂,可阻碍肿瘤从辐射损伤中恢复,被负载到PDA上。
一系列全面的体外和体内试验表明,纳米颗粒能有效被癌细胞摄取,在癌细胞中可产生活性氧并导致细胞死亡。在体内,这导致小鼠4T1癌症模型中的肿瘤体积显著减小。
此处开发的制剂在未来癌症治疗的研究和探索中具有巨大潜力。