Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug.
Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug.
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DOI：
10.1016/j.ajps.2023.100844
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发表时间：
2023-09
影响因子：
10.2
通讯作者：
Shen, Jianliang
中科院分区：
文献类型：
--
作者：
Huang, Yong;Lin, Yi;Li, Bowen;Zhang, Fu;Zhan, Chenyue;Xie, Xin;Yao, Zhuo;Wu, Chongzhi;Ping, Yuan;Shen, Jianliang
铁凋亡已成为非凋亡细胞死亡的一种有效形式，为避免凋亡途径的化疗耐药性提供了一种有前途的替代方案，并成为癌症的脆弱性。本论文构建了一种仿生自组装纳米前药系统，能够将吉非替尼（Gefi）、二茂铁（Fc）和双氢青蒿素（DHA）共递送，用于铁凋亡和细胞凋亡的联合治疗。在肿瘤微环境中，这种纳米前药能够在高水平GSH下分解并引发药物释放。有趣的是，释放的DHA可以下调GPX 4水平，以增强Fc引起的细胞内铁凋亡，进一步执行肿瘤细胞死亡，伴随吉非化疗。更重要的是，这种纳米前药通过涂覆相关细胞膜提供了高度同源的靶向能力，并表现出对肿瘤生长和转移的显著抑制，以及在治疗期间没有明显的副作用。这种简单的小分子自组装纳米前体药物为亚铁代谢联合化疗提供了一种新的合理设计的模式。基于小分子自组装的仿生纳米前药系统已被开发用于铁凋亡和细胞凋亡的联合治疗。仿生纳米前药集靶向共递送和联合治疗的优势于一体，可刺激药物在肿瘤微环境下释放，有效抑制铁凋亡抵抗增强的铁凋亡，提高不同肿瘤模型的治疗效果。
Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer. Herein, we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib (Gefi), ferrocene (Fc) and dihydroartemisinin (DHA) for the combined therapy of both ferroptosis and apoptosis. In the tumor microenvironment, this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH. Interestingly, the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc, further executing tumor cell death with concomitant chemotherapy by Gefi. More importantly, this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis, as well as no noticeable side-effects during treatments. This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy. A biomimetic nano-prodrug system based on small molecule self-assembly has been developed for the combined therapy of both ferroptosis and apoptosis. The biomimetic nano-prodrug integrates the advantage of targeted co-delivery and combination therapy, which can stimulate the release of drugs under the tumor microenvironment, effectively inhibit ferroptosis resistance for enhanced ferroptosis and improve the therapeutic effect of different tumors model.
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影响因子：
6.6
作者：
Xu, Xueming;Chen, Yuan;Li, Bowen
通讯作者：
Li, Bowen
重复剂量的二氢二甲素 - 二喹用于预防和治疗疟疾的安全性，耐受性和功效：系统评价和荟萃分析。
DOI：
10.1016/s1473-3099(16)30378-4
发表时间：
2017-02
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Gutman J;Kovacs S;Dorsey G;Stergachis A;Ter Kuile FO
通讯作者：
Ter Kuile FO
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影响因子：
10.8
作者：
Sun, Bingjun;Luo, Cong;Sun, Jin
通讯作者：
Sun, Jin
影响因子：
15
作者：
Antoszczak, Michal;Muller, Sebastian;Rodriguez, Raphael
通讯作者：
Rodriguez, Raphael
影响因子：
14.8
作者：
von Krusenstiern, A. Nikolai;Robson, Ryan N.;Qian, Naixin;Qiu, Baiyu;Hu, Fanghao;Reznik, Eduard;Smith, Nailah;Zandkarimi, Fereshteh;Estes, Verna M.;Dupont, Marcel;Hirschhorn, Tal;Shchepinov, Mikhail S.;Min, Wei;Woerpel, K. A.;Stockwell, Brent R.
通讯作者：
Stockwell, Brent R.