Zhou Huimin, Yang Jing, Li Zongheng, Feng Jie, Duan Xiaopin, Yan Chenggong, Wen Ge, Qiu Xiaozhong, Shen Zheyu
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, 1023 Shatai South Road, Guangzhou, Guangdong 510515, China; School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Guangzhou, Guangdong 510515, China.
School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Guangzhou, Guangdong 510515, China.
Acta Biomater. 2024 Sep 1;185:456-466. doi: 10.1016/j.actbio.2024.07.009. Epub 2024 Jul 14.
Calcium ions (Ca) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca, 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 m/g, which enables HMCPN17 with high drug loading capability. The Ca 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 Ca and HO, 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 HO and Ca 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.
钙离子（Ca）作为第二信使参与细胞凋亡的调控。钙超载是指细胞内Ca浓度异常升高，是导致细胞死亡的一个因素。在此，基于Ca独特的生物学效应，通过简便的水解沉淀法制备了中空介孔过氧化钙纳米粒子（HMCPN），用于无药肿瘤钙化凋亡治疗。优化后的HMCPN17平均孔径为6.4nm，比表面积为81.3m/g，使其具有高载药能力。HMCPN17在pH 6.8时的Ca释放速度比在pH 7.4时快得多，这可归因于酸触发HMCPN17转化为Ca和HO，表明HMCPN17具有pH响应分解行为。阿霉素（DOX）和/或索拉非尼（SFN）的高载药量表明HMCPN17可作为通用药物递送系统（DDS）。体外和体内实验结果证实了我们的无载药HMCPN17对肿瘤具有高钙化凋亡治疗效果，这可归因于其在肿瘤中的有效积累以及在酸性肿瘤微环境中产生HO和Ca的能力。我们的HMCPN17在构建具有多种功能的多药负载复合纳米材料用于肿瘤治疗方面具有广阔的应用前景。重要意义声明：中空介孔纳米材料与过氧化钙纳米粒子的结合在肿瘤协同治疗中具有广泛应用。在本研究中，基于简单的水解沉淀法制备了中空介孔过氧化钙纳米粒子（HMCPN）用于无药肿瘤钙化凋亡治疗。DOX和/或SFN的高载药量表明我们的HMCPN可作为通用DDS。实验结果表明，即使无载药，HMCPN对肿瘤也具有高钙化凋亡治疗效果。
