时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, the therapeutic efficacy of ferroptosis remains constrained by several intrinsic limitations.；Another major challenge lies in the insufficient availability of key substrates within the tumor microenvironment (TME).
方法
D-Luciferin, Sodium Salt (#40901ES02) and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Apoptosis Assay Kit (#40307ES50) were purchased from Yeasen (China).；Reactive Oxygen Species Assay Kit (S0033M), 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) Cell Proliferation and Cytotoxicity Assay Kit (C0009S) were purchased from Beyotime (China).；C57BL/6 mice (female, 6–8 weeks old) were purchased from Beijing Biocytogen and maintained in the Animal Center of Zhejiang University under specific pathogen-free (SPF) conditions, with a 12-h light/12-h dark cycle and free access to food and water.；RNA sequencing data (STAR-Counts, GDC harmonized) and corresponding clinical annotations for the TCGA-SKCM cohort were obtained from the UCSC Xena platform.
核心结论
Kaplan–Meier survival analysis showed that patients with higher NQO1 expression exhibited a trend toward poorer overall survival compared with those with lower expression (Fig.；To further characterize the biological processes associated with NQO1 expression, gene set enrichment analysis (GSEA) was performed by comparing NQO1-high and NQO1-low tumors within the TCGA cohort.；The analysis revealed significant enrichment of multiple oxidative stress–related pathways in NQO1-high tumors, including reactive oxygen species signaling, hypoxia responses, and angiogenesis pathways (Fig. ‖ 结论：Transcriptomic analyses further supported the activation of redox- and cell death-associated pathways, highlighting the mechanistic synergy of this nanoplatform.
局限
To address this limitation, HA was introduced via electrostatic interaction with L-Arg to generate HFSAL.；By rationally combining NQO1-activated redox cycling, Fenton chemistry, and NO generation, HFSAL effectively overcomes key limitations of conventional ferroptosis-based strategies, including insufficient oxidative stress induction, limited Fe2+ availability, and suboptimal tumor selectivity.；Future studies should further evaluate large-scale manufacturing, long-term biosafety, and therapeutic efficacy in additional clinically relevant models to facilitate clinical translation.
对本项目的价值
★☆☆☆☆ 相关范围内，作为背景与横向对照收录。
全文来源
PMC JATS 全文（正文 55,724 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Cascade-activatable nano-prodrug amplifies ROS-RNS signaling to target NQO1-associated redox vulnerability for melanoma therapy.
- 期刊与标识：J Nanobiotechnology · PMID 42958530 · DOI 10.1186/s12951-026-04825-0
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
关于本文的文献来源：本站依据 IMA 知识库「五刊监控·深度文献卡片」撰写，依据已获取的期刊全文（方法、样本量与结论已回到原文核对）；未能获取全文的同批条目另行标注「摘要级」，全程未做任何数值推算补全。