期刊
ACS NANO
卷 15, 期 5, 页码 8663-8675出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c00698
关键词
peroxynitrite; supramolecular prodrug nanoassemblies; nitric oxide; cisplatin; oxidative therapy
类别
资金
- National Natural Science Foundation of China [51773198, 21774110, 51903119, 52022090]
- Zhejiang Provincial Ten Thousand Talents Program [2018R52001]
This study reports a novel supramolecular prodrug nanoassemblies strategy that co-delivers nitric oxide and superoxide anion inducing chemotherapeutic agents for enhanced reactive nitrogen species effects in chemotherapy. The efficacy of this strategy was validated in hepatoma models, providing a new direction for cancer treatment.
The development of a controllable reactive nitrogen species (RNS) generation system for cancer treatment has remained elusive. Herein, a supramolecular prodrug nanoassemblies (SPNA) strategy that co-delivers a nitric oxide (NO) donor and a superoxide anion (O-2(center dot-)) inducing chemotherapeutic agent was reported for RNS-potentiated chemotherapy. The mole ratio of platinum(IV) prodrug and NO donor could be precisely tailored in SPNA(Pt/NO). Platinum(II) and NO would be released intracellularly to produce a highly toxic RNS, peroxynitrite anion (ONOO-). The levels of glutathione reductase (GR) and xeroderma pigmentosum group A (XPA) were down-regulated by ONOO-, thus synergistically decreasing detoxification and blocking DNA damage repair of Pt-based chemotherapy. The RNS-potentiated efficacy of SPNA(Pt/NO) was validated on subcutaneous hepatoma xenograft models and an orthotopic cisplatin-resistant hepatoma model. This co-delivery strategy of NO donor and O-2(center dot-) inducing chemotherapeutic agents for RNS-mediated therapy provides an insightful direction for cancer treatment.
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