Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui 323000, PR China.
J Control Release. 2020 Jul 10;323:578-590. doi: 10.1016/j.jconrel.2020.04.047. Epub 2020 May 5.
Therapeutic goals for rheumatoid arthritis (RA) consist of inhibiting the inflammatory response and repairing the damaged bone/cartilage. Tissue engineering could achieve both goals, however, it was hindered due to the lack of biologically relevant tissue complexity, limitation in covering the entire polyarthritis lesions and requirement of extra surgical implantation. Integrating nanotechnologies into clinically sized implants represents a major opportunity to overcome these problems. Herein, we designed a sialic acid (SA)-modified chitosan oligosaccharide-based biphasic calcium phosphate (BCP), a biomimetic nanoplatform that could load with methotrexate. We found that SA modification could not only improve the accumulation of the designed organic-inorganic nanoplatform in arthritic paws (34.38% higher than those without SA modification at 48 h), but also cooperate with BCP to exert synergetic mineralization of calcium phosphate, allowing more osteoblasts to attach, proliferate and differentiate. The more differentiated osteoblasts produced 4.46-fold type I collagen and 2.60-fold osteoprotegerin compared to the control group. Besides, the disassembled nanorods released chitosan oligosaccharide-based micelles, revealing a cartilage-protective effect by reducing the loss of glycosaminoglycan. All these improvements contributed to the light inflammatory response and reduced destruction on cartilage/bone. The findings provide a novel strategy for RA therapy via nanometer-scale dimension mimicking the natural tissues.
类风湿关节炎 (RA) 的治疗目标包括抑制炎症反应和修复受损的骨骼/软骨。组织工程可以同时实现这两个目标，但由于缺乏具有生物学相关性的组织复杂性、限制了对整个多关节炎病变的覆盖以及需要额外的外科植入，它受到了阻碍。将纳米技术整合到临床规模的植入物中代表了克服这些问题的主要机会。在此，我们设计了一种唾液酸 (SA) 修饰的壳聚糖寡糖基双相磷酸钙 (BCP)，这是一种仿生纳米平台，可以负载甲氨蝶呤。我们发现，SA 修饰不仅可以提高设计的有机-无机纳米平台在关节炎爪子中的积累（48 小时时比没有 SA 修饰的高 34.38%），还可以与 BCP 协同发挥协同矿化作用，使更多的成骨细胞附着、增殖和分化。与对照组相比，分化程度更高的成骨细胞产生了 4.46 倍的 I 型胶原和 2.60 倍的骨保护素。此外，纳米棒的解体释放出壳聚糖寡糖基胶束，通过减少糖胺聚糖的损失，显示出软骨保护作用。所有这些改进都有助于减轻炎症反应和对软骨/骨骼的破坏。这些发现为通过模仿天然组织的纳米级尺寸的 RA 治疗提供了一种新策略。
