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一种用于骨肉瘤治疗的pH响应型钛基局部给药系统。

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

作者信息

Xiao Qinle, Wan Changjun, Zhang Zhe, Liu Hui, Liu Pingting, Huang Qianli, Zhao Dapeng

机构信息

College of Biology, Hunan University, Changsha 410082, China.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083, China.

出版信息

J Funct Biomater. 2024 Oct 21;15(10):312. doi: 10.3390/jfb15100312.

Abstract

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

摘要

骨肉瘤是主要的骨癌之一,尤其是在青少年中。目前的治疗通常需要全身化疗和切除骨肿瘤。钛(Ti)基植入物可以被改造成局部药物递送(LDD)系统,用于可控和局部的化疗药物释放。在这项工作中,通过引入聚多巴胺(PDA)设计了一种pH响应性Ti基LDD原型,以在低pH值的骨肉瘤细胞周围释放阿霉素(DOX)。采用傅里叶变换红外光谱(FTIR)、扫描电子显微镜(SEM)和接触角测量仪进行表面表征。采用直接和间接细胞培养模式进行生物相容性和生物功能评估。结果表明,Ti基LDD原型表现出显著的pH依赖性DOX释放。在pH = 6.0时,72小时后的累积释放量可达约40%,而在pH = 7.4时仅约为20%。Ti基LDD植入物在体外直接培养24小时后,与MC3T3细胞具有良好的生物相容性,细胞活力约为93%。直接和间接培养模式均验证了LDD植入物具有良好的抗骨肉瘤功能,这应归因于DOX的pH响应性释放。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d037/11508615/38a66d595690/jfb-15-00312-g001.jpg

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