Mu Mengyao, Zhang Mengmeng, Liu Jie, Ren Ke, Liu Hui, Yip Lixian, Guo Kai, Teng Feifei, Dong Jian, Xu Xueli, Leong David Tai, Sun Xiao
School of Science, Shandong Jianzhu University, Jinan, 250101, China.
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, China.
Bioact Mater. 2025 Jun 4;52:63-72. doi: 10.1016/j.bioactmat.2025.05.033. eCollection 2025 Oct.
Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure. Once ineffective, patients may miss the critical window for pursuing alternative treatment options. Herein, a manganese sulfide nanoplatform loaded with proton pump inhibitor (PPI) is developed. This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging (MRI), achieving real-time therapeutic efficacy precognition. The nanoplatform releases PPI, HS, and Mn within the acidic lysosome of tumor cells. PPI inhibits V-ATPase expression, leading to an increase in intracellular H levels. HS accelerates glucose consumption of tumor cells, producing more lactic acid and further inducing tumor acidosis. Tumor acidosis in turn accelerates the nanoplatform's degradation, achieving higher tumor MRI. As the tumor acidosis degree correlates positively with tumor regression, real-time visualization of acidosis degree effectively predicts future therapeutics. Interestingly, tumor acidosis achieves efficient tumor metastasis suppression rather than increases it. Overall, this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.
传统的抗肿瘤策略通常需要足够的时间根据肿瘤结构的变化来评估疗效。一旦无效,患者可能会错过寻求其他治疗方案的关键时机。在此,开发了一种负载质子泵抑制剂(PPI)的硫化锰纳米平台。该纳米平台旨在通过磁共振成像(MRI)可视化肿瘤酸中毒程度,实现实时治疗效果预认知。纳米平台在肿瘤细胞的酸性溶酶体内释放PPI、HS和Mn。PPI抑制V-ATPase表达,导致细胞内H水平升高。HS加速肿瘤细胞的葡萄糖消耗,产生更多乳酸并进一步诱导肿瘤酸中毒。肿瘤酸中毒反过来加速纳米平台的降解,实现更高的肿瘤MRI信号。由于肿瘤酸中毒程度与肿瘤消退呈正相关,酸中毒程度的实时可视化有效地预测了未来的治疗效果。有趣的是,肿瘤酸中毒实现了有效的肿瘤转移抑制而非促进。总体而言,这项工作展示了一种能够实时可视化肿瘤酸中毒并精确预测未来治疗效果的纳米平台。