P.A. Herzen Moscow Research Oncology Institute, Branch of FSBI National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, 2nd Botkinsky Pass. 3, 125284 Moscow, Russia.
A.A. Baikov Institute of Metallurgy and Materials Science RAS, Leninsky Avenue 49, 119334 Moscow, Russia.
Int J Mol Sci. 2023 Jul 19;24(14):11633. doi: 10.3390/ijms241411633.
Bones are the fourth most frequent site of metastasis from malignant tumors, including breast cancer, prostate cancer, melanoma, etc. The bioavailability of bone tissue for chemotherapy drugs is extremely low. This requires a search for new approaches of targeted drug delivery to the tumor growth zone after surgery treatment. The aim of this work was to develop a method for octacalcium phosphate (OCP) bone graft functionalization with the cytostatic drug cisplatin to provide the local release of its therapeutic concentrations into the bone defect. OCP porous ceramic granules (OCP ceramics) were used as a platform for functionalization, and bisphosphonate zoledronic acid was used to mediate the interaction between cisplatin and OCP and enhance their binding strength. The obtained OCP materials were studied using scanning electron and light microscopy, high-performance liquid chromatography, atomic emission spectroscopy, and real-time PCR. In vitro and in vivo studies were performed on normal and tumor cell lines and small laboratory animals. The bioactivity of initial OCP ceramics was explored and the efficiency of OCP functionalization with cisplatin, zoledronic acid, and their combination was evaluated. The kinetics of drug release and changes in ceramics properties after functionalization were studied. It was established that zoledronic acid changed the physicochemical and bioactive properties of OCP ceramics and prolonged cisplatin release from the ceramics. In vitro and in vivo experiments confirmed the biocompatibility, osteoconductivity, and osteoinductivity, as well as cytostatic and antitumor properties of the obtained materials. The use of OCP ceramics functionalized with a cytostatic via the described method seems to be promising in clinics when primary or metastatic tumors of the bone tissue are removed.
骨骼是恶性肿瘤转移的第四大常见部位，包括乳腺癌、前列腺癌、黑色素瘤等。化疗药物在骨组织中的生物利用度极低。这就需要寻找新的方法，在手术后的肿瘤生长区域靶向输送药物。本工作旨在开发一种用细胞抑制剂顺铂对八钙磷酸盐（OCP）骨移植物进行功能化的方法，以提供其治疗浓度在骨缺损部位的局部释放。OCP 多孔陶瓷颗粒（OCP 陶瓷）被用作功能化的平台，并用双膦酸盐唑来膦酸来介导顺铂与 OCP 之间的相互作用，增强它们的结合强度。使用扫描电子显微镜和光学显微镜、高效液相色谱、原子发射光谱和实时 PCR 研究了获得的 OCP 材料。在正常和肿瘤细胞系以及小型实验动物上进行了体外和体内研究。探索了初始 OCP 陶瓷的生物活性，并评估了 OCP 与顺铂、唑来膦酸及其组合的功能化效率。研究了药物释放动力学和功能化后陶瓷性能的变化。结果表明，唑来膦酸改变了 OCP 陶瓷的物理化学和生物活性特性，并延长了陶瓷中顺铂的释放。体外和体内实验证实了所获得的材料具有良好的生物相容性、骨传导性和骨诱导性，以及细胞抑制和抗肿瘤特性。使用通过所述方法功能化的具有细胞抑制作用的 OCP 陶瓷，当原发性或转移性骨组织肿瘤被切除时，在临床上似乎很有前景。
