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负载淫羊藿苷的鲍鱼壳衍生镁掺杂介孔羟基磷灰石微球药物递送系统诱导骨肉瘤细胞凋亡

Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells.

作者信息

Liu Kaihua, Cheng Meiqi, Huang Hao, Yu Hui, Zhao Shiyao, Zhou Jinnuo, Tie Dan, Wang Jianhua, Pan Panpan, Chen Jingdi

机构信息

Marine College, Shandong University, Weihai, Shandong Province, China.

State Key Laboratory of Mineral Processing, Beijing, China.

出版信息

Biomater Transl. 2024 Jun 28;5(2):185-196. doi: 10.12336/biomatertransl.2024.02.008. eCollection 2024.

Abstract

Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg/ icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg substitution or coordination in the HAP lattice. At 30% Mg doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.

摘要

羟基磷灰石(HAP)多孔微球具有非常高的比表面积和载药能力,以及优异的生物相容性,已被广泛应用于肿瘤治疗。镁被认为是骨再生的关键因素,作为一种活性剂刺激骨和软骨形成,并且在加速细胞迁移和促进血管生成方面有效,这对于骨组织修复、抗癌和抗感染至关重要。在本研究中,使用来自各种来源的鲍鱼壳作为原料,通过水热合成制备了镁掺杂的鲍鱼壳衍生介孔HAP微球(Mg-HAP)作为镁/淫羊藿苷智能双递送系统(ICA-Mg-HAP,IMHA)。随着镁掺杂量的增加,HAP微球的表面形态从塌陷的大孔变为介孔再变为光滑无孔,这可能是由于镁在HAP晶格中的取代或配位。在30%镁掺杂时,Mg-HAP微球呈现出更均匀的介孔形态,具有高比表面积(186.06 m2/g)。IMHA微球显示出高载药量(7.69%)和包封率(83.29%),镁持续释放超过27天,淫羊藿苷持续稳定释放60小时,并且对pH具有良好的响应性(pH 6.4 > pH 5.6)。此外,IMHA递送系统刺激骨髓间充质干细胞的快速增殖,并通过阻断骨肉瘤细胞的G2期周期和刺激凋亡基因(Bcl-2、caspase-3、-8、-9)的高表达诱导MG63细胞凋亡。这表明基于鲍鱼壳的IMHA在药物递送和肿瘤治疗中可能具有潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c33/11438601/51572e29486a/bt-05-02-185-g001.jpg

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