Hu Ziwei, Tan Haixin, Ye Yicheng, Xu Wenxin, Gao Junbin, Liu Lu, Zhang Lishan, Jiang Jiamiao, Tian Hao, Peng Fei, Tu Yingfeng
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.
Adv Mater. 2024 Dec;36(49):e2412227. doi: 10.1002/adma.202412227. Epub 2024 Oct 6.
Ferroptosis nano-inducers have drawn considerable attention in the treatment of malignant tumors. However, low intratumoral hydrogen peroxide level and complex biological barriers hinder the ability of nanomedicines to generate sufficient reactive oxygen species (ROS) and achieve tumor penetration. Here a near-infrared (NIR)-driven ROS self-supplying nanomotor is successfully designed for synergistic tumor chemodynamic therapy (CDT) and photothermal therapy (PTT). Janus nanomotor is created by the asymmetrical modification of polydopamine (PDA) with zinc peroxide (ZnO) and subsequent ferrous ion (Fe) chelation via the polyphenol groups from the PDA, here refer as ZnO@PDA-Fe (Z@P-F). ZnO is capable of slowly releasing hydrogen peroxide (HO) into an acidic tumor microenvironment (TME) providing sufficient ingredients for the Fenton reaction necessary for ferroptosis. Upon NIR laser irradiation, the loaded Fe is released and a thermal gradient is simultaneously formed owing to the asymmetric PDA coating, thus endowing the nanomotor with self-thermophoresis based enhanced diffusion for subsequent lysosomal escape and tumor penetration. Therefore, the release of ferrous ions (Fe), self-supplied HO, and self-thermophoresis of nanomotors with NIR actuation further improve the synergistic CDT/PTT efficacy, showing great potential for active tumor therapy.
铁死亡纳米诱导剂在恶性肿瘤治疗中已引起广泛关注。然而，肿瘤内过氧化氢水平较低以及复杂的生物屏障阻碍了纳米药物产生足够的活性氧（ROS）并实现肿瘤渗透。在此，成功设计了一种近红外（NIR）驱动的ROS自供应纳米马达，用于协同肿瘤化学动力学疗法（CDT）和光热疗法（PTT）。通过用过氧化锌（ZnO）对聚多巴胺（PDA）进行不对称修饰，随后通过PDA中的多酚基团进行亚铁离子（Fe）螯合，制备了Janus纳米马达，在此称为ZnO@PDA-Fe（Z@P-F）。ZnO能够在酸性肿瘤微环境（TME）中缓慢释放过氧化氢（HO），为铁死亡所需的芬顿反应提供足够的成分。在近红外激光照射下，负载的Fe被释放，由于不对称的PDA涂层同时形成热梯度，从而赋予纳米马达基于自热泳的增强扩散能力，以便随后实现溶酶体逃逸和肿瘤渗透。因此，亚铁离子（Fe）的释放、自供应的HO以及近红外驱动的纳米马达的自热泳进一步提高了CDT/PTT协同疗效，在主动肿瘤治疗方面显示出巨大潜力。
