Table 1 Delivery ligands targeting bone matrix
From: Targeting strategies for bone diseases: signaling pathways and clinical studies
Ligand | Binding feature | Advantage | Disadvantage | Ref |
|---|---|---|---|---|
Bisphosphonate | Less influenced by the crystallinity of HAP | Higher binding ratio Intrinsic anti-resorption effect Easy conjugation with drugs or drug vectors through R1 or R2 Economic convenience | Long-term presence in HAP Side effects such as ONJ, atypical femoral fractures, esophageal cancer, and nephrotoxicity Potency to reduce the secretion of insulin-like growth factors and BMPs to promote osteoblast formation | |
Phytic acid | Less influenced by the crystallinity of HAP | Natural existing compounds in vivo Inherent antitumor and anti-osteoclastogenesis ability Reduced gastrointestinal disturbance | Low oral bioavailability | |
Tetracycline | Prefers low crystallinity HAP and growing surface | Intrinsic anti-collagenolytic ability Upregulating the expression of procollagen mRNA, thus activating more osteoblasts Strong affinity toward bone with a high remodeling rate | Teeth staining and enamel hypoplasia Dose-dependent dual effect on osteogenesis Permanent chelation Low chemical stability to conjugate with drugs or vectors | |
Acidic Oligopeptide | HAP on bone-resorbing surface | Faster binding rate Better drug release and less side effect due to high biodegradation Usage in virus vectors | Not orally bioavailable Higher drug release but lower concentration due to lysis of enzymes to linkages | |
DSS | HAP on bone formation surface | |||
Collagen-binding domain (CBD) | Collagen in bone | Easy combination for agents, cell adhesion and retention effect, especially when used in implant coating | Distribution in skin | |
WYRGRL | Collagen II | Cartilage specific | Much lower collagen II content in cartilage than skin Rely on intra-articular injection |
