Delivery

Dr. Ge Zhang's Lab has an interest in developing targeted delivery systems to accommodate specific therapeutic strategies in musculoskeletal disorders, e.g. targeted delivery systems for bone anabolic therapy/bone catabolism inhibition and intra-articular delivery systems for cartilage anabolism / cartilage catabolism inhibition. In the past five years, Dr. Ge Zhang's Lab has worked on a delivery system to facilitate osteogenic siRNAs specifically targeting osteoblasts via specifically approaching bone formation surface (tissue-specific level) (Figure 3) (Zhang Ge et al. Nature Medicine 2012), which has accommodated RNAi-based bone anabolic therapy. Recently, the lab has started to seek cell-specific delivery via screening and obtaining certain aptamer with high specificity and affinity to specific cell type (cell-specific level). The ultimate aim is to achieve a specific delivery from tissue-selective level to cell-selective level to facilitate translational medicine for targeted therapy in efficiency and safety.

Figure 3 Schematic diagrams illustrating the postulated working principle of how the (DSS)6-liposome-siRNA selectively targets bone formation surfaces.

(DSS)6 has shown the capability of preferential binding to bone formation surfaces, which are predominantly occupied by osteogenic lineage cells (osteoprogenitor cells, pre-osteoblasts, and osteoblasts) and characterized by low crystalline hydroxyapatite and amorphous calcium phosphates. These characteristics are significantly different from that of bone resorption surfaces, which are marked by high crystalline hydroxyapatite. (DSS)6 directs siRNA-entrapped liposomes mostly to bone formation surfaces, thus facilitating the interaction between the attached siRNAs and various osteogenic lineage cells.

Reference

  1. Zhang G (Corresponding Author), Guo BS, Wu H, Tang T, Zhang BT, et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nature Medicine 2012; 18: 307-14