Novel Bone-targeted Agents for Treatment of Osteoporosis

The novel bone-targeted agents were designed and synthesized by the combination of raloxifene and bisphosphonates. The anti-osteoporosis effect was evaluated by bone mineral density (BMD) obtained from OVX mice in vivo. The results indicated that the compound 8, 9 not only prevented ovariectomy induced loss of bone but also enhanced BMD to 0.87% and 19.67% compared to Sham, respectively.

Bone site-specific delivery of siRNA

Small interfering RNAs （siRNA） have enormous potential as therapeutics to target and treat various bone disor- ders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeu- tics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides （Asp）8 and （AspSerSer）6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast- specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models.

Design, Synthesis and Investigation of Bone Affinity of the Conjugates of 5-Fluorouracil and Hydroxybisphosphonate

A series of novel bone-targeting antitumor agents-the conjugates of 5-fluorouracil and hydroxybisphosphonate were designed and synthesized their structures were confirmed by ^1H-NMR, ^13C-NMR, ^31P-NMR, MS, and element analysis. The tests of bone-targeting activity show that these compounds have an obvious affinity for bone.

Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration

Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and retention.To tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone regeneration.We encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore sizes.The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation assays.The PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo.The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect animal.Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.

Current concepts and trends in the treatment of bone metastases in patients with advanced prostate cancer

Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer.These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions.Second-generation antihormona]drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases.Radiopharmaceuticals such as radium-223 dichloride([^223Ra])have been demonstrated not only to reduce skeletal-related events and bone-related pain,but also to prolong overall survival,thereby being the first bone-targeting agent showing a survival benefit.As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease,the use of these agents is not recommended.In oligometastatic prostate cancer,the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.

Recent advances in the targeted fluorescent probes for the detection of metastatic bone cancer

Tumors of the breast,prostate,and lung are most likely to metastasize to the bone and typically indicates a poor cure and survival rate in cancer patients.Detection of metastatic bone cancer in early stage would save many lives and greatly improve patients’quality of life.Clinically,bone scintigraphy is often utilized to visualize bone metastases due to its relatively low cost and high sensitivity.Recently,a growth number of analytical researches aimed at developing targeted fluorescent probes to noninvasively image bone metastases with improved spatial resolution and specificity has been reported.In this review,we will summarize and discuss the recent published fluorescent probes on the accurate detection of metastatic bone cancer.First,the design principles of various targeted probes for imaging bone metastases will be presented,highlighting the signal moieties,targeting ligands,and physicochemical properties of the bone-specific probes.Next,the up-to-date bone-targeting fluorescent probes will be summarized and overviewed.Finally,future perspectives and challenges confronting the researchers in this field will be discussed.We believe this review will encourage novel ideas to develop smart targeted molecular probes for bone metastasis imaging,image-guided surgery,and therapeutic imaging materials.