无定形纳米碳酸钙（ACC）具有比表面积大、药物负载效率高、可承载多类型药物、pH 灵敏响应、生物相容性好和生物可降解等优点，为新型药物递送系统的构建提供了广阔的发展前景。碳酸钙是岩石中常见的物质，也是海洋生物外壳、蜗牛、珍珠和蛋壳中的主要生物矿物。其中ACC是碳酸钙中最不稳定的非晶态结构，在水环境中会迅速重结晶转变为方解石和菱镁矿等稳定的晶体，因此传统的水相环境中制备稳定的ACC极具挑战性。在本研究中，我们旨在研究不同添加剂 ATP、ADP、STP、P-ser 和 Gly对ACC纳米粒子的水相稳定性的影响规律。研究根据添加剂中磷酸基团的摩尔数平衡 ATP（三磷酸腺苷, 3 个磷酸基团）、ADP（二磷酸腺苷, 2 个磷酸基团）、STP（三磷酸钠, 3 个磷酸基团）、P-ser（磷酸丝氨酸, 1 个磷酸基团）和 Gly（甘氨酸, 0 个磷酸基团）的加入量，研究探索不同添加剂 ATP、ADP 和 STP 在水溶液中稳定 ACC 纳米粒子的稳定机制。研究结果显示ATP 、STP和ADP对ACC的稳定效果远远优于P-ser和Gly，ATP-ACC 纳米粒子在全水相环境中储存 30 天依旧保持稳定的结构和晶型。机制研究结果表明，添加剂对ACC纳米粒子的稳定来自于磷酸基团的贡献，ATP-ACC展示出最优的水相稳定性。与此同时， ATP-ACC 纳米球具有良好的生物相容性和对 pH 响应的生物降解性。制备得到的稳定ACC展示出对亲水药物（阿霉素） 和疏水药物（姜黄素）的良好负载能力以及在酸性环境中的良好释放行为。高度水相环境稳定的ACC制备将推动其在生物医学领域，尤其是药物递送领域广阔的应用前景。

Amorphous nano-calcium carbonate (ACC) possesses several advantages, such as a large surface area, high drug loading efficiency, ability to carry multiple types of drugs, pH sensitivity, good biocompatibility, and biodegradability, which offer promising prospects for the development of novel drug delivery systems. Calcium carbonate is a common substance in rocks and serves as the main biomineral in the shells of marine organisms, snails, pearls, and eggshells. Among them, ACC is the most unstable amorphous structure of calcium carbonate. It quickly recrystallizes into stable crystals such as calcite and vaterite in an aqueous environment, challenging the traditional preparation of stable ACC in aqueous environments. In this study, we aimed to investigate the effect of different additives, ATP, ADP, STP, P-ser, and Gly, on the aqueous stability of ACC nanoparticles. According to the balance of the molar number of phosphate groups in the additives, ATP (3 phosphate groups), ADP (2 phosphate groups), STP (3 phosphate groups), P-ser (1 phosphate group), and Gly (0 phosphate group), the study explored the mechanism of different additives ATP, ADP, and STP in stabilizing ACC nanoparticles in aqueous solutions. The results showed that ATP, STP, and ADP had much better stabilizing effects on ACC than P-ser and Gly. ATP-ACC nanoparticles maintained a stable structure even after storage for 30 days in a fully aqueous environment. Mechanistic studies showed that the stability of ACC nanoparticles with additives came from the contribution of phosphate groups, and ATP-ACC exhibited the best aqueous stability. Meanwhile, ATP-ACC nanoparticles exhibited good biocompatibility and pH-responsive biodegradability. The prepared stable ACC demonstrated good loading capacity for both hydrophilic drugs (doxorubicin) and hydrophobic drugs (curcumin) and good release behavior in acidic environments. Preparing highly aqueous stable ACC will promote its broad application prospects in the biomedical field, especially in drug delivery.