Conventional chemotherapy leads to severe adverse effects since it involves systemic administration of toxic drugs at high dosage. Unlike traditional chemotherapeutics, calcium phosphate and citrate have both been discussed as very promising anticancer agents and are not inherently toxic. Yet, their breakthrough has been hampered by the lack of an administration approach that overcomes the strict regulatory mechanisms of the cell. Here, we present a combinatorial administration of calcium, phosphate, and citrate as colloidal, amorphous nanoparticles (CPCs) that selectively kill cancer cells without involvement of inherently toxic drugs. The particles are toxic neither before endosomal release nor after their degradation. This highly selective toxicity allowed us to successfully treat two different aggressive pleural tumors in mice, reducing their size by about 40% and 70% after only two local applications. Safety assessment studies over 2 months show no signs of adverse effects except for slightly enhanced pleural thickening after eight applications.

常规化学疗法会导致严重的不良反应，因为它涉及高剂量全身性给药有毒药物。与传统的化学疗法不同，磷酸钙和柠檬酸钙都被认为是非常有前途的抗癌药，并且本身没有毒性。然而，由于缺乏克服细胞严格调节机制的管理方法，阻碍了它们的突破。在这里，我们介绍了钙，磷酸盐和柠檬酸盐的组合给药，它们是胶体，无定形纳米颗粒（CPC），可选择性杀死癌细胞而不涉及固有毒性的药物。颗粒在内体释放之前或降解后均无毒。这种高度选择性的毒性使我们能够成功治疗小鼠中两种不同的侵袭性胸膜肿瘤，仅两次本地应用后，它们的大小分别减小了40％和70％。超过2个月的安全性评估研究表明，除八次应用后胸膜增厚略有增强外，没有任何不良反应的迹象。