关键词: biocompatibility cartilage differentiation chondrodysplasia controlled release nanoplatforms

Mesh : Animals Magnesium Silicon Zebrafish Cartilage Cartilage Diseases Power, Psychological

来  源:   DOI:10.2147/IJN.S446552   PDF(Pubmed)

Abstract:
UNASSIGNED: Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.
UNASSIGNED: A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the \"dissolution-regrowth\" method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.
UNASSIGNED: A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.
UNASSIGNED: The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
摘要:
软骨相关疾病,如发育不良的软骨发育不良是一种罕见的遗传性疾病,会影响新生儿,导致软骨发育异常和骨骼生长受限。然而,由于受控药物递送的局限性,软骨发育不良的有效治疗策略的开发仍然面临重大挑战,生物相容性,和纳米药物的生物降解性。
构建了基于硅纳米颗粒(MON)的可生物降解的镁掺杂的硅基纳米平台。简而言之,使用MPTMS用巯基修饰MON以形成MOS。通过“溶解-再生长”方法掺入Mg2离子,实现了MOS的进一步工程,导致MMOS。Ica被有效地加载到MMOS通道中,并将HA锚定在MOS的表面以获得MMOS-Ica@HA纳米平台。此外,使用体外细胞实验和体内斑马鱼胚胎模型来评估纳米平台对软骨分化或形成的影响以及治疗软骨发育不良的效率。
一系列表征测试,包括TEM,SEM,DLS,XPS,EDX,和BET分析验证了MOS-Ica@HA纳米平台的成功制备。制备的纳米平台表现出优异的分散性和可控的药物释放行为。细胞毒性评价揭示了MOS-Ica@HA由于Ica的持续和可控释放而具有良好的生物相容性。重要的是,MOS-Ica@HA中Ica和Mg成分的存在通过Smad5/HIF-1α信号通路显著促进BMSCs的软骨分化。体外和体内实验证实,纳米平台通过促进软骨分化和形成来改善软骨发育不良。
研究结果表明,开发的可生物降解的MMOS-Ica@HA纳米平台具有可接受的载药量和受控的药物释放在软骨发育不良治疗中的潜在应用,这表明了治疗软骨发育不良的有希望的方法。
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