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 ...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.展开更多
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 elemen...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.展开更多
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 metastas...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.展开更多
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 ...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.展开更多
基金supported by the Cancer Prevention Research Institute of Texas(CPRIT,RP 150656,X.L.)National Institute of Health(NIH/NCI,R15CA182769, X.L.)
文摘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.
文摘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.
文摘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.
基金This work was supported by the National Natural Science Foundation of China(21907054)the Fundamental Research Funds from Nankai University(ZB19100136)+2 种基金the National Institutes of Health(NIH)National Institute of Biomedical Imaging and Bioengineering(NIBIB)(R01 EB025192-01A1)the Cancer Prevention and Research Institute of Texas(CPRIT)(RP190251)the Welch Foundation(I-1855).
文摘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.