Yang Tao, Zhang Qinglei, Miao Yao, Lyu Yang, Xu Yajing, Yang Mingying, Mao Chuanbin
School of Materials Science & Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. China.
Department of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, P. R. China.
Adv Mater. 2025 Jan;37(2):e2403756. doi: 10.1002/adma.202403756. Epub 2024 Sep 5.
Photodynamic therapy (PDT) eliminates cancer cells by converting endogenous oxygen into reactive oxygen species (ROS). However, its efficacy is significantly hindered by hypoxia in solid tumors. Hence, to engineer filamentous fd phage, a human-friendly bacteria-specific virus is proposed, into a nanozyme-nucleating photosensitizer-loaded tumor-homing nanofiber for enhanced production of ROS in a hypoxic tumor. Specifically, Pt-binding and tumor-homing peptides are genetically displayed on the sidewall and tip of the fd phage, respectively. The Pt-binding peptides induced nucleation and orientation of Pt nanozymes (PtNEs) on the sidewall of the phage. The resultant PtNE-coated tumor-homing phage exhibits significantly enhanced sustained catalytic conversion of hydrogen peroxide in hypoxic tumors into O for producing ROS needed for PDT, compared to non-phage-templated PtNE. Density functional theory (DFT) calculations verify the catalytic mechanism of the phage-templated PtNE. After intravenous injection of the PtNE-coated indocyanine green (ICG)-loaded tumor-homing phages into breast tumor-bearing mice, the nanofibers home to the tumors and effectively inhibit tumor growth by the PtNE-enhanced PDT. The nanofibers can also serve as a tumor-homing imaging probe due to the fluorescence of ICG. This work demonstrates that filamentous phage, engineered to become tumor-homing nanozyme-nucleating tumor-hypoxia-relieving nanofibers, can act as cancer-targeting nanozymes with improved catalytic performance for effective targeted PDT.
光动力疗法（PDT）通过将内源性氧转化为活性氧（ROS）来消除癌细胞。然而，实体瘤中的缺氧显著阻碍了其疗效。因此，有人提出将丝状fd噬菌体（一种对人类友好的细菌特异性病毒）改造成一种负载纳米酶成核光敏剂的肿瘤归巢纳米纤维，以增强缺氧肿瘤中ROS的产生。具体而言，与铂结合的肽和肿瘤归巢肽分别通过基因工程展示在fd噬菌体的侧壁和尖端。与铂结合的肽诱导铂纳米酶（PtNEs）在噬菌体侧壁上成核并定向排列。与非噬菌体模板化的PtNE相比，所得的包被PtNE的肿瘤归巢噬菌体在缺氧肿瘤中表现出显著增强的将过氧化氢持续催化转化为氧气以产生PDT所需ROS的能力。密度泛函理论（DFT）计算验证了噬菌体模板化PtNE的催化机制。将包被PtNE的负载吲哚菁绿（ICG）的肿瘤归巢噬菌体静脉注射到荷乳腺肿瘤小鼠体内后，纳米纤维归巢到肿瘤部位，并通过PtNE增强的PDT有效抑制肿瘤生长。由于ICG的荧光，纳米纤维还可以作为肿瘤归巢成像探针。这项工作表明，经过工程改造成为肿瘤归巢纳米酶成核肿瘤缺氧缓解纳米纤维的丝状噬菌体，可以作为具有改善催化性能的癌症靶向纳米酶，用于有效的靶向PDT。
