Dysfunction of DNA repair for boosted tumor cell cycle arrest based on NIR-II biodegradable Te-prussian blue nanorod

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2023-01, Vol.455, p.140870, Article 140870
• Main Authors: Liang, Xiaoyang, Liu, Ping, Li, Wen, Binh Vong, Long, Wang, Tingting, Geng, Lujing, Zhou, Yue, Wang, Siyu, Lu, Qiang, Tan, Fengping, Wang, Xinxing, Li, Nan
• Format: Article
• Language: English
• Subjects: Biodegradation; Cell cycle arrest; DNA repair dysfunction; Homoharringtonine; Oxidative stress; Tellurium
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2022.140870

•We prepared Te@PB@PDA-HA/HHT NRs with a highly biodegradation efficiency.•Te@PB@PDA-HA/HHT NRs exhibited good NIR-II photothermal activity.•Dysfunction of DNA repair boosted cell cycle arrest in tumor. Reactive oxygen species (ROS)-mediated cell cycle arrest mechanism shows distinguished potential for the inhibiting of cancer cells. However, poly ADP-ribose polymerase (PARP), an enzyme which can contribute to the repair of single-strand DNA nicks, largely limited the efficiency in cell cycle arrest. Here, polydopamine (PDA)/hyaluronic acid (HA) decorated and protein translation inhibitor homoharringtonine (HHT) loaded tellurium (Te)-prussian blue (PB) nanorods (Te@PB@PDA-HA/HHT NRs) were synthesized for boosted G2 cell cycle arrest to realize tumor ablation. Under NIR-II irradiation, Te and Fe elements can collectively generate ROS and deplete GSH due to the fenton-like reaction and metal-reducing reaction under tumor microenvironment (TME), thus disturbing the DNA structure to induce cell cycle arrest. More importantly, HHT suppresses PARP production to induce DNA repair dysfunction, thereby boosting DNA oxidative damage. Remarkably, this nanoplatform degrades into ionic form under acid condition, illustrating inherently TME-responsive biodegradability. The anti-tumor evaluation illustrated that Te@PB@PDA-HA/HHT NRs could notably destroy tumor cells in both cellular experiments and mouse models. This study made a successful attempt in boosted cell cycle arrest and encouraged more biological explorations on biodegradation nanomaterials, especially in combating cancers.