Potassium Iodide Nanoparticles Enhance Radiotherapy against Breast Cancer by Exploiting the Sodium-Iodide Symporter.
Potassium Iodide Nanoparticles Enhance Radiotherapy against Breast Cancer by Exploiting the Sodium-Iodide Symporter.
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碘化钾纳米粒子通过利用钠-碘转运体增强乳腺癌放射治疗。
DOI：
10.1021/acsnano.1c01435
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发表时间：
2021-11-23
期刊：
影响因子：
17.1
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Cline BL;Jiang W;Lee C;Cao Z;Yang X;Zhan S;Chong H;Zhang T;Han Z;Wu X;Yao L;Wang H;Zhang W;Li Z;Xie J
碘在增强放射治疗方面显示出希望。然而，传统的碘化合物显示出快速清除和癌细胞内的低保留，限制了它们作为放射增敏剂的应用。在此，我们合成了聚（马来酸酐-alt-1-十八烯）涂层KI纳米粒子（PMAO-KI NPs），并评估其增强放射治疗的潜力。由于聚合物涂层，PMAO-KI NP的KI核心不会立即溶解在水溶液中，而是缓慢降解，从而实现碘化物（I-）的受控释放。I-通过钠碘同向转运体（NIS）转运到细胞中，在乳腺癌细胞中被上调。我们的研究结果表明，PMAO-KI纳米颗粒可以增强辐射诱导的活性氧物种，如羟基自由基的产生。当在体外用MCF-7细胞进行测试时，PMAO-KI NP促进辐射诱导的DNA双链断裂和脂质过氧化，导致癌细胞活力和繁殖力下降。当在携带MCF-7的小鼠中测试时，PMAO-KI NP显示出显著的放射增敏作用，导致80%的治疗动物中的肿瘤完全根除，而不诱导额外的毒性。总的来说，我们的策略利用电解质纳米颗粒通过NIS将碘化物递送到癌细胞中，从而促进针对乳腺癌的放射治疗。
Iodine has shown promise in enhancing radiotherapy. However, conventional iodine compounds show fast clearance and low retention inside cancer cells, limiting their application as a radiosensitizer. Herein, we synthesize poly(maleic anhydride-alt-1-octadecene) coated KI nanoparticles (PMAO-KI NPs) and evaluate their potential for enhancing radiotherapy. Owing to the polymer coating, the KI core of PMAO-KI NPs is not instantly dissolved in aqueous solutions but slowly degraded, allowing for controlled release of iodide (I−). I− is transported into cells via the sodium iodide symporter (NIS), which is upregulated in breast cancer cells. Our results show that PMAO-KI NPs can enhance radiation-induced production of reactive oxygen species such as hydroxyl radicals. When tested in vitro with MCF-7 cells, PMAO-KI NPs promote radiation-induced DNA double-strand breaks and lipid peroxidation, causing a drop in cancer cell viability and reproductivity. When tested in MCF-7 bearing mice, PMAO-KI NPs show significant radiosensitizing effects, leading to complete tumor eradication in 80% of the treated animals without inducing additional toxicity. Overall, our strategy exploits electrolyte nanoparticles to deliver iodide into cancer cells through NIS, thus promoting radiotherapy against breast cancer.
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