Yu Min, Chen Zeming, Guo Wenjun, Wang Jin, Feng Yupeng, Kong Xiuqi, Hong Zhangyong
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
Int J Nanomedicine. 2015 Mar 4;10:1743-57. doi: 10.2147/IJN.S75950. eCollection 2015.
Macrophages play important roles in the pathogenesis of various diseases, and are important potential therapeutic targets. Furthermore, macrophages are key antigen-presenting cells and important in vaccine design. In this study, we report on the novel formulation (bovine serum albumin [BSA]-loaded glucan particles [GMP-BSA]) based on β-glucan particles from cell walls of baker's yeast for the targeted delivery of protein to macrophages. Using this formulation, chitosan, tripolyphosphate, and alginate were used to fabricate colloidal particles with the model protein BSA via electrostatic interactions, which were caged and incorporated BSA very tightly within the β-glucan particle shells. The prepared GMP-BSA exhibited good protein-release behavior and avoided protein leakage. The particles were also highly specific to phagocytic macrophages, such as Raw 264.7 cells, primary bone marrow-derived macrophages, and peritoneal exudate macrophages, whereas the particles were not taken up by nonphagocytic cells, including NIH3T3, AD293, HeLa, and Caco-2. We hypothesize that these tightly encapsulated protein-loaded glucan particles deliver various types of proteins to macrophages with notably high selectivity, and may have broad applications in targeted drug delivery or vaccine design against macrophages.
巨噬细胞在多种疾病的发病机制中发挥着重要作用，是重要的潜在治疗靶点。此外，巨噬细胞是关键的抗原呈递细胞，在疫苗设计中也很重要。在本研究中，我们报道了一种基于面包酵母细胞壁β-葡聚糖颗粒的新型制剂（负载牛血清白蛋白[BSA]的葡聚糖颗粒[GMP-BSA]），用于将蛋白质靶向递送至巨噬细胞。使用该制剂，壳聚糖、三聚磷酸钠和海藻酸盐通过静电相互作用与模型蛋白BSA制备胶体颗粒，该胶体颗粒将BSA紧密包裹并纳入β-葡聚糖颗粒壳内。制备的GMP-BSA表现出良好的蛋白质释放行为并避免了蛋白质泄漏。这些颗粒对吞噬性巨噬细胞（如Raw 264.7细胞、原代骨髓来源的巨噬细胞和腹腔渗出巨噬细胞）也具有高度特异性，而包括NIH3T3、AD293、HeLa和Caco-2在内的非吞噬细胞不会摄取这些颗粒。我们推测，这些紧密包裹的负载蛋白质的葡聚糖颗粒能够以显著的高选择性将各种类型的蛋白质递送至巨噬细胞，并且可能在针对巨噬细胞的靶向药物递送或疫苗设计中具有广泛应用。
