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The development of controllable reactive nitrogen species (RNS) generation systems for cancer treatment still faces challenges. Here, Ji Jian, Jinqiao of Zhejiang University, and Zhou Dongfang of Southern Medical University jointly reported a supramolecular prodrug nano-assembly (SPNA) strategy that co-delivers nitric oxide (NO) donors and can induce the production of superoxide anions (O2). •–) chemotherapeutic drugs are used for liver cancer chemotherapy enhanced by reactive nitrogen. The molar ratio of platinum (IV) prodrug and NO donor can be precisely controlled by SPNA Pt/NO. Platinum (II) and NO will be released in cells, producing highly toxic RNS, peroxynitrite anion (ONOO-). ONOO- can down-regulate the levels of glutathione reductase (GR) and DNA damage repair protein XPA, thereby synergistically reducing tumor repair of DNA damage caused by platinum drugs. The efficacy of SPNA Pt/NO was verified on subcutaneous xenograft liver cancer models and orthotopic cisplatin-resistant liver cancer models. This strategy of combined administration of NO donors and O2•-induction chemotherapeutics provides an insightful direction for RNS-mediated tumor therapy.

Yongyan Deng, Tailoring Supramolecular Prodrug Nanoassemblies for Reactive Nitrogen Species-Potentiated Chemotherapy of Liver Cancer, ACS Nano, 2021.

DOI: 10.1021/acsnano.1c00698

https://doi.org/10.1021/acsnano.1c00698