Hydroxyapatite (HA) nanoparticles are commonly used as building blocks in the design of bone-substituting biomaterials. Recently, these nanoparticles have been considered for the treatment of metastasis disease, since their pH-dependent dissolution behavior allows for precise tuning of release kinetics of loaded cargo. Herein we show that the capacity of drug-loaded nanoparticles stabilized with citrate ions reduce cancer cell survival in an embryonic zebrafish xenograft model. In particular, in vitro studies demonstrate that PtPP-loaded HA nanoparticles exhibit anti–proliferative activity against breast cancer cells at reduced pH. In vivo studies using an embryonic zebrafish xenograft model reveal that PtPP co-delivered with human breast cancer cells strongly reduce cancer cell survival. Similarly, co-injection of breast cancer cells with citrate-functionalized and PtPP-loaded HA nanoparticles into zebrafish significantly reduces survival of cancer cells due to release of chemotherapeutically active kiteplatin species. These results demonstrate the preclinical efficacy of drug-loaded nanoparticles against human breast cancer cells in a xenogenic embryonic in vivo model.

中文翻译：

---

斑马鱼异种移植模型中铂负载羟基磷灰石纳米粒子的临床前评估。

羟基磷灰石（HA）纳米粒子通常用作替代骨的生物材料设计的基础。最近，由于它们的pH依赖性溶解行为可以精确调节装载货物的释放动力学，因此已经考虑将这些纳米颗粒用于转移性疾病的治疗。本文中，我们显示了用柠檬酸根离子稳定的载药纳米颗粒的容量会降低胚胎斑马鱼异种移植模型中癌细胞的存活率。特别是，体外研究表明，在降低的pH值下，载有PtPP的HA纳米颗粒对乳腺癌细胞具有抗增殖活性。体内使用胚胎斑马鱼异种移植模型进行的研究表明，与人乳腺癌细胞共同递送的PtPP大大降低了癌细胞的存活率。同样，将乳腺癌细胞与柠檬酸盐官能化的和PtPP加载的HA纳米颗粒共同注射到斑马鱼中，由于释放出具有化学治疗活性的kiteplatin物种，因此大大降低了癌细胞的存活率。这些结果证明了异种胚胎体内模型中载药纳米粒子对人乳腺癌细胞的临床前功效。