{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:34:36Z","timestamp":1790678076759,"version":"4.1.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Targeted delivery by either systemic or local targeting of therapeutics to the bone is an attractive treatment for various bone metabolism diseases such as osteoporosis, osteoarthritis, osteosarcoma, osteomyelitis, etc. To overcome the limitations of direct drug delivery, the combination of bone-targeted agents with nanotechnology has the opportunity to provide a more effective therapeutic approach, where engineered nanoparticles cause the drug to accumulate in the bone, thereby improving efficacy and minimizing side effects. Here, we summarize the current advances in systemic or local bone-targeting approaches and nanosystem applications in bone diseases, which may provide new insights into nanocarrier-delivered drugs for the targeted treatment of bone diseases. We envision that novel drug delivery carriers developed based on nanotechnology will be a potential vehicle for the treatment of currently incurable bone diseases and are expected to be translated into clinical applications.<\/jats:p>","DOI":"10.3389\/fphar.2022.909408","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T08:21:00Z","timestamp":1653985260000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":77,"title":["Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Yulin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14191","DOI":"10.1039\/c5nr02730f","article-title":"Smart Multifunctional Drug Delivery towards Anticancer Therapy Harmonized in Mesoporous Nanoparticles","volume":"7","author":"Baek","year":"2015","journal-title":"Nanoscale"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1021\/ar500217w","article-title":"Photocontrolled Nanoparticle Delivery Systems for Biomedical Applications","volume":"47","author":"Bansal","year":"2014","journal-title":"Acc. Chem. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jconrel.2015.07.018","article-title":"Ultraviolet Light-Mediated Drug Delivery: Principles, Applications, and Challenges","volume":"219","author":"Barhoumi","year":"2015","journal-title":"J. Control Release"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1016\/s0140-6736(11)60243-2","article-title":"Osteoarthritis: an Update with Relevance for Clinical Practice","volume":"377","author":"Bijlsma","year":"2011","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1056\/NEJMcp1513724","article-title":"Clinical Practice. Postmenopausal Osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.actbio.2019.03.010","article-title":"Intra-articular Targeting of Nanomaterials for the Treatment of Osteoarthritis","volume":"93","author":"Brown","year":"2019","journal-title":"Acta Biomater."},{"key":"B7","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3109\/03008208909002412","article-title":"The Nature and Significance of Osteopontin","volume":"23","author":"Butler","year":"1989","journal-title":"Connect. Tissue Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"113884","DOI":"10.1016\/j.addr.2021.113884","article-title":"Drug Delivery Carriers with Therapeutic Functions","volume":"176","author":"Cai","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1016\/j.biomaterials.2007.12.022","article-title":"Biocompatibility of poly(D,L-lactide-co-glycolide) Nanoparticles Conjugated with Alendronate","volume":"29","author":"Cenni","year":"2008","journal-title":"Biomaterials"},{"key":"B10","doi-asserted-by":"publisher","first-page":"119520","DOI":"10.1016\/j.biomaterials.2019.119520","article-title":"Cartilage-targeting and Dual MMP-13\/pH Responsive Theranostic Nanoprobes for Osteoarthritis Imaging and Precision Therapy","volume":"225","author":"Chen","year":"2019","journal-title":"Biomaterials"},{"key":"B11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bioactmat.2022.01.048","article-title":"The Horizon of Bone Organoid: A Perspective on Construction and Application","volume":"18","author":"Chen","year":"2022","journal-title":"Bioact. Mater"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/gels7040199","article-title":"Bone Regeneration Using MMP-Cleavable Peptides-Based Hydrogels","volume":"7","author":"Chen","year":"2021","journal-title":"Gels"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.drudis.2017.04.021","article-title":"Development of Nanomaterials for Bone-Targeted Drug Delivery","volume":"22","author":"Cheng","year":"2017","journal-title":"Drug Discov. Today"},{"key":"B14","doi-asserted-by":"publisher","first-page":"121818","DOI":"10.1016\/j.talanta.2020.121818","article-title":"Aptamer Selection and Aptasensor Construction for Bone Density Biomarkers","volume":"224","author":"Chinnappan","year":"2021","journal-title":"Talanta"},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jconrel.2007.06.003","article-title":"Design of Surface-Modified poly(D,L-lactide-co-glycolide) Nanoparticles for Targeted Drug Delivery to Bone","volume":"122","author":"Choi","year":"2007","journal-title":"J. Control Release"},{"key":"B16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.coph.2006.03.005","article-title":"Recent Advances in Understanding the Mechanism of Action of Bisphosphonates","volume":"6","author":"Coxon","year":"2006","journal-title":"Curr. Opin. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1242\/jcs.063032","article-title":"Bone Remodelling at a Glance","volume":"124","author":"Crockett","year":"2011","journal-title":"J. Cell Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6149","DOI":"10.1111\/jcmm.15229","article-title":"Triptolide Prevents Bone Loss via Suppressing Osteoclastogenesis through Inhibiting PI3K-AKT-NFATc1 Pathway","volume":"24","author":"Cui","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.bioactmat.2021.09.015","article-title":"A Bone-Targeted Engineered Exosome Platform Delivering siRNA to Treat Osteoporosis","volume":"10","author":"Cui","year":"2022","journal-title":"Bioact. Mater"},{"key":"B20","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1097\/00005131-200205000-00009","article-title":"Fluorescent Tetracycline Labeling as an Aid to Debridement of Necrotic Bone in the Treatment of Chronic Osteomyelitis","volume":"16","author":"Dahners","year":"2002","journal-title":"J. Orthop. Trauma"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4697","DOI":"10.1016\/j.bioactmat.2021.04.038","article-title":"Bone-targeted pH-Responsive Cerium Nanoparticles for Anabolic Therapy in Osteoporosis","volume":"6","author":"Dou","year":"2021","journal-title":"Bioact. Mater"},{"key":"B22","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1021\/nl903411s","article-title":"Photo-targeted Nanoparticles","volume":"10","author":"Dvir","year":"2010","journal-title":"Nano Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.bone.2011.03.774","article-title":"The Relationship between the Chemistry and Biological Activity of the Bisphosphonates","volume":"49","author":"Ebetino","year":"2011","journal-title":"Bone"},{"key":"B24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jot.2020.07.006","article-title":"Defining Disease Progression in Chinese Mainland People: Association between Bone Mineral Density and Knee Osteoarthritis","volume":"26","author":"Fang","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1706759","DOI":"10.1002\/adma.201706759","article-title":"Cell Membrane Coating Nanotechnology","volume":"30","author":"Fang","year":"2018","journal-title":"Adv. Mater"},{"key":"B26","doi-asserted-by":"publisher","first-page":"7357","DOI":"10.1021\/acsami.8b18820","article-title":"Engineering of Bone- and CD44-Dual-Targeting Redox-Sensitive Liposomes for the Treatment of Orthotopic Osteosarcoma","volume":"11","author":"Feng","year":"2019","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.3390\/polym13152464","article-title":"Advances in Functionalized Photosensitive Polymeric Nanocarriers","volume":"13","author":"Fern\u00e1ndez","year":"2021","journal-title":"Polymers"},{"key":"B28","doi-asserted-by":"publisher","first-page":"421746","DOI":"10.1155\/2015\/421746","article-title":"Biology of Bone Tissue: Structure, Function, and Factors that Influence Bone Cells","volume":"2015","author":"Florencio-Silva","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0167-4838(95)00190-5","article-title":"Acidic Amino Acid-Rich Sequences as Binding Sites of Osteonectin to Hydroxyapatite Crystals","volume":"1292","author":"Fujisawa","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"B30","doi-asserted-by":"publisher","first-page":"787118","DOI":"10.3389\/fcell.2021.787118","article-title":"Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation","volume":"9","author":"Gao","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/s41571-021-00519-8","article-title":"Advancing Therapy for Osteosarcoma","volume":"18","author":"Gill","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.canlet.2016.12.012","article-title":"Doxorubicin and Edelfosine Lipid Nanoparticles Are Effective Acting Synergistically against Drug-Resistant Osteosarcoma Cancer Cells","volume":"388","author":"Gonz\u00e1lez-Fern\u00e1ndez","year":"2017","journal-title":"Cancer Lett."},{"key":"B33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.biomaterials.2015.05.001","article-title":"Dual-targeting and pH\/redox-Responsive Multi-Layered Nanocomplexes for Smart Co-delivery of Doxorubicin and siRNA","volume":"60","author":"Han","year":"2015","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3358","DOI":"10.1039\/c5cs00118h","article-title":"Wavelength-selective Cleavage of Photoprotecting Groups: Strategies and Applications in Dynamic Systems","volume":"44","author":"Hansen","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","article-title":"Osteoporosis: Impact on Health and Economics","volume":"6","author":"Harvey","year":"2010","journal-title":"Nat. Rev. Rheumatol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.2165\/00003088-200342150-00002","article-title":"Bone-specific Drug Delivery Systems: Approaches via Chemical Modification of Bone-Seeking Agents","volume":"42","author":"Hirabayashi","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jot.2020.04.006","article-title":"Osteoporosis and Osteoarthritis: A Translational Perspective","volume":"22","author":"Hopkins","year":"2020","journal-title":"J. Orthop. Transl."},{"key":"B38","doi-asserted-by":"publisher","first-page":"120819","DOI":"10.1016\/j.biomaterials.2021.120819","article-title":"Bone Targeting Nanocarrier-Assisted Delivery of Adenosine to Combat Osteoporotic Bone Loss","volume":"273","author":"Hoque","year":"2021","journal-title":"Biomaterials"},{"key":"B39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41413-021-00147-z","article-title":"Subchondral Bone Microenvironment in Osteoarthritis and Pain","volume":"9","author":"Hu","year":"","journal-title":"Bone Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1016\/j.bioactmat.2021.02.014","article-title":"Exosome-guided Bone Targeted Delivery of Antagomir-188 as an Anabolic Therapy for Bone Loss","volume":"6","author":"Hu","year":"","journal-title":"Bioact. Mater"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/s0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1200\/jco.2014.59.4895","article-title":"Osteosarcoma: Current Treatment and a Collaborative Pathway to Success","volume":"33","author":"Isakoff","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"101487","DOI":"10.1016\/j.nantod.2022.101487","article-title":"Engineered Extracellular Vesicles for Bone Therapy","volume":"44","author":"Jiang","year":"2022","journal-title":"Nano Today"},{"key":"B44","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12951-020-00651-0","article-title":"Intra-articular Delivery of Celastrol by Hollow Mesoporous Silica Nanoparticles for pH-Sensitive Anti-inflammatory Therapy against Knee Osteoarthritis","volume":"18","author":"Jin","year":"2020","journal-title":"J. Nanobiotechnology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.2147\/IJN.S125231","article-title":"Anti-FGFR1 Aptamer-Tagged Superparamagnetic Conjugates for Anticancer Hyperthermia Therapy","volume":"12","author":"Jurek","year":"2017","journal-title":"Int. J. Nanomedicine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cbi.2018.07.016","article-title":"Thermo- and pH Dual Responsive Polymeric Micelles and Nanoparticles","volume":"295","author":"Kalhapure","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"B47","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nrc3838","article-title":"Translational Biology of Osteosarcoma","volume":"14","author":"Kansara","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2020.08.014","article-title":"\"Hard\" Ceramics for \"Soft\" Tissue Engineering: Paradox or Opportunity?","volume":"115","author":"Kargozar","year":"2020","journal-title":"Acta Biomater."},{"key":"B49","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1136\/annrheumdis-2013-204111","article-title":"The Coupling of Bone and Cartilage Turnover in Osteoarthritis: Opportunities for Bone Antiresorptives and Anabolics as Potential Treatments?","volume":"73","author":"Karsdal","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1359\/jbmr.2000.15.5.936","article-title":"Selective Drug Delivery System to Bone: Small Peptide (Asp)6 Conjugation","volume":"15","author":"Kasugai","year":"2000","journal-title":"J. Bone Min. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/s2213-8587(17)30188-2","article-title":"Osteoporosis Treatment: Recent Developments and Ongoing Challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/s0031-3955(16)32087-9","article-title":"The Tetracyclines","volume":"15","author":"Kunin","year":"1968","journal-title":"Pediatr. Clin. North Am."},{"key":"B53","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.bioactmat.2021.06.027","article-title":"Multifunctional GelMA Platforms with Nanomaterials for Advanced Tissue Therapeutics","volume":"8","author":"Kurian","year":"2022","journal-title":"Bioact. Mater"},{"key":"B54","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12951-020-00666-7","article-title":"MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis","volume":"18","author":"Lan","year":"2020","journal-title":"J. Nanobiotechnology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"110862","DOI":"10.1016\/j.msec.2020.110862","article-title":"Temperature- and pH-Responsive Chitosan-Based Injectable Hydrogels for Bone Tissue Engineering","volume":"111","author":"Lavanya","year":"2020","journal-title":"Mater Sci. Eng. C Mater Biol. Appl."},{"key":"B56","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jconrel.2018.01.021","article-title":"Stimuli-responsive Nanocarriers for Delivery of Bone Therapeutics - Barriers and Progresses","volume":"273","author":"Lavrador","year":"2018","journal-title":"J. Control Release"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.897539","article-title":"Stat3 Signaling Pathway: A Future Therapeutic Target for Bone-Related Diseases","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jot.2021.04.005","article-title":"The Role of Osteocytes-specific Molecular Mechanism in Regulation of Mechanotransduction - A Systematic Review","volume":"29","author":"Li","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1080\/10717544.2020.1785049","article-title":"Co-delivery of Doxorubicin and Paclitaxel by reduction\/pH Dual Responsive Nanocarriers for Osteosarcoma Therapy","volume":"27","author":"Li","year":"2020","journal-title":"Drug Deliv."},{"key":"B60","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nm.3791","article-title":"Aptamer-functionalized Lipid Nanoparticles Targeting Osteoblasts as a Novel RNA Interference-Based Bone Anabolic Strategy","volume":"21","author":"Liang","year":"2015","journal-title":"Nat. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/8756-3282(95)00445-9","article-title":"Bisphosphonates: a Review of Their Pharmacokinetic Properties","volume":"18","author":"Lin","year":"1996","journal-title":"Bone"},{"key":"B62","doi-asserted-by":"publisher","first-page":"17543","DOI":"10.1021\/jacs.0c07309","article-title":"Smart Nanosacrificial Layer on the Bone Surface Prevents Osteoporosis through Acid-Base Neutralization Regulated Biocascade Effects","volume":"142","author":"Lin","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176380","article-title":"Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment","volume":"21","author":"Liu","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.bioactmat.2021.12.006","article-title":"Bacterial Extracellular Vesicles as Bioactive Nanocarriers for Drug Delivery: Advances and Perspectives","volume":"14","author":"Liu","year":"","journal-title":"Bioact. Mater"},{"key":"B65","doi-asserted-by":"publisher","first-page":"63","DOI":"10.20517\/evcna.2022.04","article-title":"Engineered Mammalian and Bacterial Extracellular Vesicles as Promising Nanocarriers for Targeted Therapy","volume":"3","author":"Liu","year":"","journal-title":"Extracell. Vesicles Circ. Nucleic Acids"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1016\/j.addr.2013.09.019","article-title":"Nanomedicine Therapeutic Approaches to Overcome Cancer Drug Resistance","volume":"65","author":"Markman","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B67","doi-asserted-by":"publisher","first-page":"4900","DOI":"10.1002\/anie.200600387","article-title":"Biologically Active Molecules with a \"light Switch\"","volume":"45","author":"Mayer","year":"2006","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B68","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nrrheum.2017.219","article-title":"Osteoarthritis in 2017: Latest Advances in the Management of Knee OA","volume":"14","author":"McAlindon","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.amjmed.2012.06.023","article-title":"Bisphosphonate Therapy for Osteoporosis: Benefits, Risks, and Drug Holiday","volume":"126","author":"McClung","year":"2013","journal-title":"Am. J. Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.tibtech.2015.07.001","article-title":"Biomimetic Particles as Therapeutics","volume":"33","author":"Meyer","year":"2015","journal-title":"Trends Biotechnol."},{"key":"B71","first-page":"87","article-title":"Bone Localization of the Tetracyclines","volume":"19","author":"Milch","year":"1957","journal-title":"J. Natl. Cancer Inst."},{"key":"B72","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/nmat3776","article-title":"Stimuli-responsive Nanocarriers for Drug Delivery","volume":"12","author":"Mura","year":"2013","journal-title":"Nat. Mater"},{"key":"B73","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.bmcl.2008.12.051","article-title":"Bone Selective Effect of an Estradiol Conjugate with a Novel Tetracycline-Derived Bone-Targeting Agent","volume":"19","author":"Neale","year":"2009","journal-title":"Bioorg Med. Chem. Lett."},{"key":"B74","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1515\/hsz-2013-0292","article-title":"Tetracycline Antibiotics and Resistance Mechanisms","volume":"395","author":"Nguyen","year":"2014","journal-title":"Biol. Chem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.2147\/IJN.S78498","article-title":"Poly(lactic-co-glycolic Acid) Nanoparticles Conjugated with CD133 Aptamers for Targeted Salinomycin Delivery to CD133+ Osteosarcoma Cancer Stem Cells","volume":"10","author":"Ni","year":"2015","journal-title":"Int. J. Nanomedicine"},{"key":"B76","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1146\/annurev.med.56.062904.144915","article-title":"Aptamers: an Emerging Class of Therapeutics","volume":"56","author":"Nimjee","year":"2005","journal-title":"Annu. Rev. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.bone.2012.08.121","article-title":"Osteocyte Control of Osteoclastogenesis","volume":"54","author":"O'Brien","year":"2013","journal-title":"Bone"},{"key":"B78","doi-asserted-by":"publisher","first-page":"8819","DOI":"10.1073\/pnas.83.23.8819","article-title":"Cloning and Sequence Analysis of Rat Bone Sialoprotein (Osteopontin) cDNA Reveals an Arg-Gly-Asp Cell-Binding Sequence","volume":"83","author":"Oldberg","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B79","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s00223-017-0294-z","article-title":"Histological Evaluation of Bone Repair with Hydroxyapatite: A Systematic Review","volume":"101","author":"Oliveira","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1517\/17425247.2015.1021679","article-title":"Bisphosphonate-modified Biomaterials for Drug Delivery and Bone Tissue Engineering","volume":"12","author":"Ossipov","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"B81","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jconrel.2015.12.024","article-title":"pH-responsive Polymer-Drug Conjugates: Design and Progress","volume":"222","author":"Pang","year":"2016","journal-title":"J. Control Release"},{"key":"B82","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/208787a0","article-title":"Binding of Tetracyclines to Bone","volume":"208","author":"Perrin","year":"1965","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1080\/00325481.1984.11698793","article-title":"Tetracycline's Effects on Teeth Preclude Uses in Children and Pregnant or Lactating Women","volume":"76","author":"Peterson","year":"1984","journal-title":"Postgrad. Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3181\/00379727-186-42590a","article-title":"Bone-targeted Carbonic Anhydrase Inhibitors: Effect of a Proinhibitor on Bone Resorption In Vitro","volume":"186","author":"Pierce","year":"1987","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2165\/00003088-199936050-00002","article-title":"Pharmacokinetics of Alendronate","volume":"36","author":"Porras","year":"1999","journal-title":"Clin. Pharmacokinet."},{"key":"B86","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1146\/annurev.med.46.1.249","article-title":"Treatment of Osteoporosis","volume":"46","author":"Prestwood","year":"1995","journal-title":"Annu. Rev. Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1302\/2046-3758.910.BJR-2020-0097.R1","article-title":"Bone Mineral as a Drug-Seeking Moiety and a Waste Dump","volume":"9","author":"Raina","year":"2020","journal-title":"Bone Jt. Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.addr.2021.01.009","article-title":"Targeting Drug Delivery with Light: A Highly Focused Approach","volume":"171","author":"Rapp","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B89","doi-asserted-by":"publisher","first-page":"820468","DOI":"10.3389\/fbioe.2021.820468","article-title":"Reactive Oxygen Species (ROS)-Responsive Biomaterials for the Treatment of Bone-Related Diseases","volume":"9","author":"Ren","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1126\/science.289.5484.1508","article-title":"Therapeutic Approaches to Bone Diseases","volume":"289","author":"Rodan","year":"2000","journal-title":"Science"},{"key":"B91","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jconrel.2017.11.009","article-title":"Drug Delivery Systems Functionalized with Bone Mineral Seeking Agents for Bone Targeted Therapeutics","volume":"269","author":"Rotman","year":"2018","journal-title":"J. Control Release"},{"key":"B92","doi-asserted-by":"publisher","first-page":"S150","DOI":"10.1542\/peds.2006-2023H","article-title":"Bisphosphonates: Mode of Action and Pharmacology","volume":"119","author":"Russell","year":"2007","journal-title":"Pediatrics"},{"key":"B93","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of Action of Bisphosphonates: Similarities and Differences and Their Potential Influence on Clinical Efficacy","volume":"19","author":"Russell","year":"2008","journal-title":"Osteoporos. Int."},{"key":"B94","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.jconrel.2016.04.025","article-title":"Bone-targeted Delivery of Nanodiamond-Based Drug Carriers Conjugated with Alendronate for Potential Osteoporosis Treatment","volume":"232","author":"Ryu","year":"2016","journal-title":"J. Control Release"},{"key":"B95","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1111\/j.1365-4632.2004.02108.x","article-title":"Tetracycline and Other Tetracycline-Derivative Staining of the Teeth and Oral Cavity","volume":"43","author":"Sanchez","year":"2004","journal-title":"Int. J. Dermatol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.1056\/NEJMra053077","article-title":"Bone Quality-Tthe Material and Structural Basis of Bone Strength and Fragility","volume":"354","author":"Seeman","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/nprot.2010.66","article-title":"Development of DNA Aptamers Using Cell-SELEX","volume":"5","author":"Sefah","year":"2010","journal-title":"Nat. Protoc."},{"key":"B98","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3109\/10611860108997922","article-title":"Novel Drug Delivery System to Bone Using Acidic Oligopeptide: Pharmacokinetic Characteristics and Pharmacological Potential","volume":"9","author":"Sekido","year":"2001","journal-title":"J. Drug Target"},{"key":"B99","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.addr.2004.12.017","article-title":"Skeletal Function and Structure: Implications for Tissue-Targeted Therapeutics","volume":"57","author":"Shea","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B100","doi-asserted-by":"publisher","first-page":"104825","DOI":"10.1016\/j.nanoen.2020.104825","article-title":"A Strawberry-like Ag-Decorated Barium Titanate Enhances Piezoelectric and Antibacterial Activities of Polymer Scaffold","volume":"74","author":"Shuai","year":"2020","journal-title":"Nano Energy"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2021.130145","article-title":"Self-assembling Peptide Hydrogels Facilitate Vascularization in Two-Component Scaffolds","volume":"422","author":"Siddiqui","year":"2021","journal-title":"Chem. Eng. J."},{"key":"B102","doi-asserted-by":"publisher","first-page":"2041731419877528","DOI":"10.1177\/2041731419877528","article-title":"Advances in Nanoparticle Development for Improved Therapeutics Delivery: Nanoscale Topographical Aspect","volume":"10","author":"Singh","year":"2019","journal-title":"J. Tissue Eng."},{"key":"B103","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1021\/acs.nanolett.9b00287","article-title":"Reversal of Osteoporotic Activity by Endothelial Cell-Secreted Bone Targeting and Biocompatible Exosomes","volume":"19","author":"Song","year":"2019","journal-title":"Nano Lett."},{"key":"B104","doi-asserted-by":"publisher","first-page":"863","DOI":"10.2165\/00003088-200342100-00001","article-title":"Bone as an Effect Compartment : Models for Uptake and Release of Drugs","volume":"42","author":"Stepensky","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"B105","doi-asserted-by":"publisher","first-page":"5759","DOI":"10.1021\/acsnano.5b07828","article-title":"Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA\/microRNA Delivery","volume":"10","author":"Sun","year":"2016","journal-title":"ACS Nano"},{"key":"B106","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/bf02408616","article-title":"Tetracycline Labeling of Bone In Vivo","volume":"30","author":"Tam","year":"1980","journal-title":"Calcif. Tissue Int."},{"key":"B107","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jconrel.2020.11.059","article-title":"Water\/pH Dual Responsive In Situ Calcium Supplement Collaborates Simvastatin for Osteoblast Promotion Mediated Osteoporosis Therapy via Oral Medication","volume":"329","author":"Tao","year":"2021","journal-title":"J. Control Release"},{"key":"B108","doi-asserted-by":"publisher","first-page":"34630","DOI":"10.1021\/acsami.0c08992","article-title":"Bone-Targeting Prodrug Mesoporous Silica-Based Nanoreactor with Reactive Oxygen Species Burst for Enhanced Chemotherapy","volume":"12","author":"Tong","year":"2020","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B109","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.addr.2004.12.011","article-title":"Bone-targeting Macromolecular Therapeutics","volume":"57","author":"Wang","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B110","first-page":"18151","article-title":"Identification of a Novel Molecular Probe for Recognition of Human Osteosarcoma Cell Using the Cell-SELEX Method","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00815-9","article-title":"Genetically Engineered and Enucleated Human Mesenchymal Stromal Cells for the Targeted Delivery of Therapeutics to Diseased Tissue","volume":"2021","author":"Wang","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1007\/s00198-009-0925-y","article-title":"Osteoporosis in china","volume":"20","author":"Wang","year":"2009","journal-title":"Osteoporos. Int."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1210\/jc.2009-1947","article-title":"Long-term Use of Bisphosphonates in Osteoporosis","volume":"95","author":"Watts","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B114","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jot.2019.10.012","article-title":"Extracellular Vesicles: Potential Role in Osteoarthritis Regenerative Medicine","volume":"21","author":"Wu","year":"2020","journal-title":"J. Orthop. Transl."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1080\/10717544.2017.1347966","article-title":"Atorvastatin-loaded Micelles with Bone-Targeted Ligand for the Treatment of Osteoporosis","volume":"24","author":"Xie","year":"2017","journal-title":"Drug Deliv."},{"key":"B116","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.actbio.2019.05.027","article-title":"Osteogenic and pH Stimuli-Responsive Self-Healing Coating on Biomedical Mg-1Ca Alloy","volume":"92","author":"Xiong","year":"","journal-title":"Acta Biomater."},{"key":"B117","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.actbio.2019.04.045","article-title":"A pH-Sensitive Self-Healing Coating for Biodegradable Magnesium Implants","volume":"98","author":"Xiong","year":"","journal-title":"Acta Biomater."},{"key":"B118","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s12951-021-00945-x","article-title":"Cartilage-targeting Poly(ethylene Glycol) (PEG)-formononetin (FMN) Nanodrug for the Treatment of Osteoarthritis","volume":"19","author":"Xiong","year":"2021","journal-title":"J. Nanobiotechnol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1016\/j.bioactmat.2021.01.017","article-title":"Cartilage-targeting Peptide-Modified Dual-Drug Delivery Nanoplatform with NIR Laser Response for Osteoarthritis Therapy","volume":"6","author":"Xue","year":"","journal-title":"Bioact. Mater"},{"key":"B120","doi-asserted-by":"publisher","first-page":"2009432","DOI":"10.1002\/adfm.202009432","article-title":"Recent Advances in Design of Functional Biocompatible Hydrogels for Bone Tissue Engineering","volume":"31","author":"Xue","year":"","journal-title":"Adv. Funct. Mat."},{"key":"B121","doi-asserted-by":"publisher","first-page":"109855","DOI":"10.1016\/j.compositesb.2022.109855","article-title":"Neutrophil-erythrocyte Hybrid Membrane-Coated Hollow Copper Sulfide Nanoparticles for Targeted and Photothermal\/Anti-inflammatory Therapy of Osteoarthritis","volume":"237","author":"Xue","year":"2022","journal-title":"Compos. Part B Eng."},{"key":"B122","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.3390\/ijms13033341","article-title":"Generating Aptamers by Cell-SELEX for Applications in Molecular Medicine","volume":"13","author":"Ye","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1210\/endo.142.3.8024","article-title":"Selective Delivery of Estradiol to Bone by Aspartic Acid Oligopeptide and its Effects on Ovariectomized Mice","volume":"142","author":"Yokogawa","year":"2001","journal-title":"Endocrinology"},{"key":"B124","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nm.2617","article-title":"A Delivery System Targeting Bone Formation Surfaces to Facilitate RNAi-Based Anabolic Therapy","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"B125","doi-asserted-by":"publisher","first-page":"100223","DOI":"10.1016\/j.mtbio.2022.100223","article-title":"Advanced Application of Stimuli-Responsive Drug Delivery System for Inflammatory Arthritis Treatment","volume":"14","author":"Zhang","year":"2022","journal-title":"Mater Today Bio"},{"key":"B126","doi-asserted-by":"publisher","first-page":"1700821","DOI":"10.1002\/advs.201700821","article-title":"Self-Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma","volume":"5","author":"Zhang","year":"","journal-title":"Adv. Sci. (Weinh)"},{"key":"B127","doi-asserted-by":"publisher","first-page":"4806","DOI":"10.1007\/s12274-018-2066-0","article-title":"Tumor Microenvironment-Responsive Hyaluronate-Calcium Carbonate Hybrid Nanoparticle Enables Effective Chemotherapy for Primary and Advanced Osteosarcomas","volume":"11","author":"Zhang","year":"","journal-title":"Nano Res."},{"key":"B128","doi-asserted-by":"publisher","first-page":"8749","DOI":"10.1021\/acsami.8b19094","article-title":"A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering","volume":"11","author":"Zhao","year":"2019","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B129","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1021\/acs.biomac.8b00422","article-title":"Photoresponsive Drug\/Gene Delivery Systems","volume":"19","author":"Zhou","year":"2018","journal-title":"Biomacromolecules"},{"key":"B130","doi-asserted-by":"publisher","first-page":"2005215","DOI":"10.1002\/adma.202005215","article-title":"Tailored Mesoporous Inorganic Biomaterials: Assembly, Functionalization, and Drug Delivery Engineering","volume":"33","author":"Zou","year":"2021","journal-title":"Adv. Mat."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.909408\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T08:21:07Z","timestamp":1653985267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.909408\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":130,"alternative-id":["10.3389\/fphar.2022.909408"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.909408","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,31]]},"article-number":"909408"}}