钙离子（Ca2+）作为第二信使参与细胞凋亡的调节。钙超载是指细胞内Ca2+浓度异常升高，是导致细胞死亡的一个因素。在此，基于Ca2+的独特生物效应，通过简便的水解-沉淀方法开发了中空介孔过氧化钙纳米颗粒（HMCPN），用于无药物治疗肿瘤钙崩解症。优化后的HMCPN17平均孔径为6.4 nm，比表面积为81.3 m2/g，使得HMCPN17具有高载药能力。 HMCPN17 在 pH 6.8 时的 Ca2 释放速度比在 pH 7.4 时快得多，这可归因于 HMCPN17 酸触发转化为 Ca2 和 H2O2，表明 HMCPN17 具有 pH 响应性分解行为。阿霉素 (DOX) 和/或索拉非尼 (SFN) 的高载药量表明 HMCPN17 可用作通用药物递送系统 (DDS)。体外和体内结果证实了我们的 HMCPN17 在无药物负载的情况下对肿瘤的高钙崩解治疗功效，这可归因于肿瘤中的有效积累以及在酸性 TME 下产生 H2O2 和 Ca2 的能力。我们的HMCPN17在构建具有多种功能的多载药复合纳米材料治疗肿瘤方面具有广阔的应用前景。意义声明：中空介孔纳米材料与过氧化钙纳米粒子的组合在肿瘤的协同治疗中具有广泛的应用。在这项研究中，基于简单的水解沉淀方法开发了中空介孔过氧化钙纳米粒子（HMCPN），用于无药物装载的肿瘤钙崩解治疗。 DOX 和/或 SFN 的高载药量表明我们的 HMCPN 可以作为通用 DDS。实验结果证明，即使在没有药物负载的情况下，HMCPN 对肿瘤的钙崩解也具有很高的治疗效果。版权所有 © 2024。由 Elsevier Ltd 出版。

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H2O2, indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H2O2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. STATEMENT OF SIGNIFICANCE: The combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading.Copyright © 2024. Published by Elsevier Ltd.