Platinum prodrug nanoparticles inhibiting tumor recurrence and metastasis by concurrent chemoradiotherapy.
Platinum prodrug nanoparticles inhibiting tumor recurrence and metastasis by concurrent chemoradiotherapy.
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DOI：
10.1186/s12951-022-01322-y
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发表时间：
2022-03-12
影响因子：
10.2
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Jiang W;Wei L;Chen B;Luo X;Xu P;Cai J;Hu Y
同步放化疗（CRT）作为临床最有效的抗肿瘤治疗方法之一，虽然可以成功地抑制肿瘤细胞的生长，但继发性肿瘤的发生风险仍然是临床实践中不可逾越的障碍。本文在Fe2O3纳米颗粒（NPs）表面合成了一种由单宁酸（TA）和Pt2+ (TA- pt)络合膜组成的新型铂前药，具有良好的稳定性和生物相容性。在该系统中，TA-Pt复合物能够响应肿瘤酸性微环境，破坏肿瘤细胞的DNA。此外，内部铁核不仅提高了后续放疗（RT）的效果，而且破坏了细胞内的铁平衡，诱导细胞内铁凋亡，消除了抗凋亡细胞。体外和体内实验结果表明，90%以上的肿瘤细胞被耗尽，75%以上的治愈荷瘤小鼠无复发和转移。本研究为有效化疗、RT和铁上吊联合治疗提高CRT疗效，抑制肿瘤复发转移提供了新的思路。在线版本包含补充材料，可在10.1186/s12951-022-01322-y获得。
Although concurrent chemoradiotherapy (CRT), as one of the most effective antineoplastic therapies in clinic, can successfully inhibit the growth of tumor cells, a risk of developing secondary tumor is still an insurmountable barrier in clinical practice. Herein, a new platinum prodrug composed of tannic acid (TA) and Pt2+ (TA-Pt) complex film was synthesized on the surface of Fe2O3 nanoparticles (NPs) with excellent stability and biocompatibility for enhanced CRT. In this system, TA-Pt complex could respond to the tumor acidic microenvironment and damage the DNA of tumor cells. Moreover, the internal iron core not only improved the effect of subsequent radiotherapy (RT), but also disrupted the iron balance in cells, inducing intracellular ferroptosis and eliminating apoptosis-resistant cells. In vitro and vivo experimental results indicated that more than 90% of tumor cells were depleted and more than 75% of the cured tumor-bearing mice evinced no recurrence or metastasis. This work offered a new idea for combining the effective chemotherapy, RT and ferroptosis therapy to enhance the curative effect of CRT and inhibit tumor recurrence and metastasis. The online version contains supplementary material available at 10.1186/s12951-022-01322-y.
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