{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:49:54Z","timestamp":1786740594371,"version":"build-2736575974"},"reference-count":64,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/G03737X\/1"],"award-info":[{"award-number":["EP\/G03737X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We show the first example of a synergic approach of oxidant (ROS) scavenging carrier and ROS-responsive drug release in the context of a potential therapy against osteoporosis, aiming to inhibit the differentiation of inflammatory cells into osteoclasts. In our \u201ctandem\u201d approach, a branched amphiphilic, PEGylated polysulfide (PPSES\u2013PEG) was preferred over a linear analogue, because of improved homogeneity in the aggregates (spherical micelles vs mixture of wormlike and spherical), increased stability, and higher drug loading (up to \u223c22 wt % of antiosteoclastic rapamycin). These effects are ascribed to the branching inhibiting crystallization in the polysulfide blocks. The ROS-scavenging micelles alone were already able to reduce osteoclastogenesis in a RAW 264.7 model, but the \u201cdrug\u201d combination (the polymer itself + rapamycin released only under oxidation) completely abrogated the process. An important take-home message is that the synergic performance depended very strongly on the oxidant:oxidizable group molar ratio, a parameter to carefully tune in the perspective of targeting specific diseases.<\/jats:p>","DOI":"10.1021\/acs.biomac.9b01348","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T08:44:22Z","timestamp":1575362662000},"page":"305-318","source":"Crossref","is-referenced-by-count":30,"title":["\u201cTandem\u201d\nNanomedicine Approach against\nOsteoclastogenesis: Polysulfide Micelles Synergically Scavenge ROS\nand Release Rapamycin"],"prefix":"10.1021","volume":"21","author":[{"given":"Farah","family":"El Mohtadi","sequence":"first","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, United Kingdom, M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"d\u2019Arcy","sequence":"additional","affiliation":[{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Burke","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, United Kingdom, M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-1458","authenticated-orcid":true,"given":"Julio M.","family":"Rios De La Rosa","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, United Kingdom, M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Gennari","sequence":"additional","affiliation":[{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Marotta","sequence":"additional","affiliation":[{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Francini","sequence":"additional","affiliation":[{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Donno","sequence":"additional","affiliation":[{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4879-3949","authenticated-orcid":true,"given":"Nicola","family":"Tirelli","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, United Kingdom, M13 9PL"]},{"name":"Fondazione Istituto Italiano di Tecnologia , , ,","place":["Genova, Italy, 16163"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"issue":"8","key":"2026081416133167700_cit1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.molmed.2014.06.001","article-title":"Osteoclasts: more than \u2019bone eaters\u2019","volume":"20","author":"Charles","year":"2014","journal-title":"Trends Mol. Med."},{"issue":"9527","key":"2026081416133167700_cit2","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1016\/S0140-6736(06)68891-0","article-title":"Osteoporosis","volume":"367","author":"Sambrook","year":"2006","journal-title":"Lancet"},{"key":"2026081416133167700_cit3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4248\/BR201301003","article-title":"Osteoclasts:\nNew Insights","volume":"1","author":"Xu","year":"2013","journal-title":"Bone\nRes."},{"key":"2026081416133167700_cit4","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.bonr.2016.07.005","article-title":"Hospitalizations for\nosteoporosis-related fractures: Economic costs and clinical outcomes","volume":"5","author":"Weycker","year":"2016","journal-title":"Bone Rep."},{"issue":"2","key":"2026081416133167700_cit5","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1055\/s-0038-1660790","article-title":"Osteoporosis: Current Concepts","volume":"6","author":"Akkawi","year":"2018","journal-title":"Joints"},{"issue":"2","key":"2026081416133167700_cit6","first-page":"92","article-title":"Osteoporosis: A Review\nof Treatment Options","volume":"43","author":"Tu","year":"2018","journal-title":"Pharm. Ther."},{"issue":"1\u20132","key":"2026081416133167700_cit7","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s11657-013-0136-1","article-title":"Osteoporosis in the European Union:\nmedical management,\nepidemiology and economic burden. A report prepared in collaboration\nwith the International Osteoporosis Foundation (IOF) and the European\nFederation of Pharmaceutical Industry Associations (EFPIA)","volume":"8","author":"Hernlund","year":"2013","journal-title":"Arch. Osteoporos."},{"issue":"24","key":"2026081416133167700_cit8","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1001\/jama.2018.7498","article-title":"Screening for osteoporosis\nto prevent fractures: Us\npreventive services task force recommendation statement","volume":"319","author":"Curry","year":"2018","journal-title":"JAMA"},{"issue":"S6","key":"2026081416133167700_cit9","first-page":"S164","article-title":"Osteoporosis\nand the burden of osteoporosis-related fractures","volume":"17","author":"Dempster","year":"2011","journal-title":"Am. J. Manag. Care"},{"issue":"4","key":"2026081416133167700_cit10","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":"2026081416133167700_cit11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.bonr.2018.06.007","article-title":"Bisphosphonate conjugation\nfor bone specific drug targeting","volume":"9","author":"Farrell","year":"2018","journal-title":"Bone Rep."},{"issue":"9","key":"2026081416133167700_cit12","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1517\/17425247.2015.1021679","article-title":"Bisphosphonate-modified\nbiomaterials for drug delivery and bone tissue engineering","volume":"12","author":"Ossipov","year":"2015","journal-title":"Expert Opin. Drug Delivery"},{"key":"2026081416133167700_cit13","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.ijcard.2016.04.088","article-title":"Adverse\ncardiovascular effects of nitrogen-containing bisphosphonates in patients\nwith osteoporosis: A nationwide population-based retrospective study","volume":"215","author":"Wang","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"2026081416133167700_cit14","unstructured":"U.S. Food and\nDrug Administration\n          . FDA Drug Safety\nCommunication: Safety update\nfor osteoporosis drugs, bisphosphonates, and atypical fractures-Safety\nAnnouncement; 2010."},{"key":"2026081416133167700_cit15","doi-asserted-by":"publisher","first-page":"38014","DOI":"10.1038\/srep38014","article-title":"NADPH oxidase gp91\u00ad(phox) contributes to RANKL-induced osteoclast\ndifferentiation by upregulating NFATc1","volume":"6","author":"Kang","year":"2016","journal-title":"Sci.\nRep."},{"issue":"8","key":"2026081416133167700_cit16","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab\nfor prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"issue":"11","key":"2026081416133167700_cit17","doi-asserted-by":"publisher","first-page":"818","DOI":"10.7326\/M15-1361","article-title":"for the Clinical\nGuidelines Committee of the American College of, P., Treatment of\nlow bone density or osteoporosis to prevent fractures in men and women:\nA clinical practice guideline update from the American college of\nphysicians","volume":"166","author":"Qaseem","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"2026081416133167700_cit18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.bone.2017.08.003","article-title":"Discontinuation\nof Denosumab therapy for osteoporosis: A systematic review and position\nstatement by ECTS","volume":"105","author":"Tsourdi","year":"2017","journal-title":"Bone"},{"issue":"10","key":"2026081416133167700_cit19","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.molmed.2009.08.004","article-title":"Oxidative\nstress in bone remodelling and disease","volume":"15","author":"Wauquier","year":"2009","journal-title":"Trends\nMol. Med."},{"issue":"2","key":"2026081416133167700_cit20","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1210\/en.2004-1021","article-title":"Hydrogen\nPeroxide Is Essential for Estrogen-Deficiency Bone Loss and Osteoclast\nFormation","volume":"146","author":"Lean","year":"2005","journal-title":"Endocrinology"},{"issue":"18","key":"2026081416133167700_cit21","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1128\/MCB.00293-14","article-title":"TRP14 Inhibits Osteoclast\nDifferentiation via Its Catalytic Activity","volume":"34","author":"Hong","year":"2014","journal-title":"Mol. Cell. Biol."},{"issue":"3","key":"2026081416133167700_cit22","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","article-title":"A crucial role for\nreactive oxygen species in RANKL-induced osteoclast differentiation","volume":"106","author":"Lee","year":"2005","journal-title":"Blood"},{"issue":"11","key":"2026081416133167700_cit23","doi-asserted-by":"publisher","first-page":"4731","DOI":"10.1172\/JCI67603","article-title":"NADPH oxidase\n4 limits bone mass by promoting osteoclastogenesis","volume":"123","author":"Goettsch","year":"2013","journal-title":"J. Clin. Invest."},{"issue":"1-2","key":"2026081416133167700_cit24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2152\/jmi.56.33","article-title":"NADPH oxidase-derived reactive oxygen\nspecies are essential for differentiation of a mouse macrophage cell\nline (RAW264.7) into osteoclasts","volume":"56","author":"Sasaki","year":"2009","journal-title":"J. Med. Invest."},{"key":"2026081416133167700_cit25","doi-asserted-by":"publisher","first-page":"8016","DOI":"10.1038\/srep08016","article-title":"Manganese superoxide\ndismutase is required to maintain osteoclast\ndifferentiation and function under static force","volume":"5","author":"Guo","year":"2015","journal-title":"Sci. Rep."},{"key":"2026081416133167700_cit26","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast\ndifferentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"issue":"1","key":"2026081416133167700_cit27","doi-asserted-by":"publisher","first-page":"1800699","DOI":"10.1002\/marc.201800699","article-title":"Oxidation-Responsive Materials: Biological\nRationale, State of the Art, Multiple Responsiveness, and Open Issues","volume":"40","author":"El-Mohtadi","year":"2019","journal-title":"Macromol. Rapid Commun."},{"key":"2026081416133167700_cit28","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.biomaterials.2014.11.016","article-title":"ROS-responsive\nmicrospheres for on demand antioxidant therapy in a model of diabetic\nperipheral arterial disease","volume":"41","author":"Poole","year":"2015","journal-title":"Biomaterials"},{"issue":"19","key":"2026081416133167700_cit29","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1002\/macp.201200264","article-title":"Oxidant-Dependent REDOX\nResponsiveness\nof Polysulfides","volume":"213","author":"Carampin","year":"2012","journal-title":"Macromol. Chem. Phys."},{"issue":"4","key":"2026081416133167700_cit30","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1039\/c3py01475d","article-title":"Chemical specificity\nin REDOX-responsive materials: the diverse effects of different Reactive\nOxygen Species (ROS) on polysulfide nanoparticles","volume":"5","author":"Jeanmaire","year":"2014","journal-title":"Polym. Chem."},{"issue":"8","key":"2026081416133167700_cit31","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1351\/pac200880081703","article-title":"Oxidation-responsiveness\nof nanomaterials for targeting\ninflammatory reactions","volume":"80","author":"Khutoryanskiy","year":"2008","journal-title":"Pure Appl. Chem."},{"key":"2026081416133167700_cit32","doi-asserted-by":"publisher","first-page":"1900038","DOI":"10.1002\/adtp.201900038","article-title":"Reactive Oxygen Species-Responsive\nNanoparticles for the Treatment of Ischemic Stroke","volume":"2","author":"Rajkovic","year":"2019","journal-title":"Adv. Therap."},{"issue":"42","key":"2026081416133167700_cit33","doi-asserted-by":"publisher","first-page":"14896","DOI":"10.1021\/ja507626y","article-title":"Cell Protective, ABC Triblock Polymer-Based Thermoresponsive\nHydrogels with ROS-Triggered Degradation and Drug Release","volume":"136","author":"Gupta","year":"2014","journal-title":"J. Am. Chem. Soc."},{"issue":"19\u201320","key":"2026081416133167700_cit34","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1089\/ten.tea.2016.0495","article-title":"Reactive Oxygen\nSpecies Shielding Hydrogel for the Delivery of Adherent and Nonadherent\nTherapeutic Cell Types","volume":"23","author":"Dollinger","year":"2017","journal-title":"Tissue Eng., Part A"},{"issue":"43","key":"2026081416133167700_cit35","doi-asserted-by":"publisher","first-page":"5098","DOI":"10.1002\/adma.201103349","article-title":"Physically Associated\nSynthetic Hydrogels with Long-Term Covalent Stabilization for Cell\nCulture and Stem Cell Transplantation","volume":"23","author":"Zhang","year":"2011","journal-title":"Adv.\nMater."},{"key":"2026081416133167700_cit36","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jconrel.2018.05.006","article-title":"Accelerated wound healing by injectable\nstar poly\u00ad(ethylene glycol)-b-poly\u00ad(propylene sulfide) scaffolds loaded\nwith poorly water-soluble drugs","volume":"282","author":"Zhu","year":"2018","journal-title":"J. Controlled\nRelease"},{"issue":"4","key":"2026081416133167700_cit37","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1021\/acsbiomaterials.6b00804","article-title":"Drug-Free ROS Sponge\nPolymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical\nInjury","volume":"4","author":"O\u2019Grady","year":"2018","journal-title":"ACS Biomater. Sci. Eng."},{"issue":"9","key":"2026081416133167700_cit38","doi-asserted-by":"publisher","first-page":"8600","DOI":"10.1021\/acsnano.7b03426","article-title":"Core-Cross-Linked\nNanoparticles Reduce Neuroinflammation\nand Improve Outcome in a Mouse Model of Traumatic Brain Injury","volume":"11","author":"Yoo","year":"2017","journal-title":"ACS Nano"},{"issue":"6","key":"2026081416133167700_cit39","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1016\/j.stemcr.2017.04.005","article-title":"Bone Size and Quality\nRegulation: Concerted Actions of mTOR in Mesenchymal Stromal Cells\nand Osteoclasts","volume":"8","author":"Wu","year":"2017","journal-title":"Stem Cell Rep."},{"issue":"1","key":"2026081416133167700_cit40","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s42003-018-0028-4","article-title":"mTORC1 impedes osteoclast\ndifferentiation via calcineurin and NFATc1","volume":"1","author":"Huynh","year":"2018","journal-title":"Commun. Biol."},{"key":"2026081416133167700_cit41","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fcell.2017.00054","article-title":"Regulation of Osteoclast Growth and Fusion by mTOR\/raptor\nand mTOR\/rictor\/Akt","volume":"5","author":"Tiedemann","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"issue":"6","key":"2026081416133167700_cit42","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1039\/C8TB02980F","article-title":"The polymerization\nkinetics, oxidation-responsiveness, and in vitro anticancer efficacy\nof poly\u00ad(ester-thioether)\u00ads","volume":"7","author":"Cheng","year":"2019","journal-title":"J. Mater. Chem. B"},{"issue":"10","key":"2026081416133167700_cit43","doi-asserted-by":"publisher","first-page":"1900171","DOI":"10.1002\/mabi.201900171","article-title":"Polymer Structure-Guided\nSelf-Assisted Preparation of Poly\u00ad(ester-thioether)-Based Hollow Porous\nMicrospheres and Hierarchically Interconnected Microcages for Drug\nRelease","volume":"19","author":"Cheng","year":"2019","journal-title":"Macromol. Biosci."},{"key":"2026081416133167700_cit44","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.jconrel.2019.08.038","article-title":"Systemic\ndelivery of a Gli inhibitor via polymeric nanocarriers inhibits tumor-induced\nbone disease","volume":"311\u2013312","author":"Vanderburgh","year":"2019","journal-title":"J. Controlled Release"},{"issue":"2","key":"2026081416133167700_cit45","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1039\/C8BM01224E","article-title":"Celastrol-loaded\nPEG-b-PPS nanocarriers as an anti-inflammatory treatment for atherosclerosis","volume":"7","author":"Allen","year":"2019","journal-title":"Biomater. Sci."},{"issue":"22","key":"2026081416133167700_cit46","doi-asserted-by":"publisher","first-page":"8108","DOI":"10.1021\/acs.macromol.5b02007","article-title":"Influence of Primary\nStructure on Responsiveness. Oxidative, Thermal, and Thermo-Oxidative\nResponses in Polysulfides","volume":"48","author":"d\u2019Arcy","year":"2015","journal-title":"Macromolecules"},{"issue":"23","key":"2026081416133167700_cit47","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1002\/marc.201600481","article-title":"Linear, Star, and Comb\nOxidation-Responsive Polymers: Effect of Branching Degree and Topology\non Aggregation and Responsiveness","volume":"37","author":"d\u2019Arcy","year":"2016","journal-title":"Macromol.\nRapid Commun."},{"issue":"1","key":"2026081416133167700_cit49","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1021\/ma00079a018","article-title":"Polystyrene poly\u00ad(methacrylic acid) block-copolymer micelles","volume":"27","author":"Qin","year":"1994","journal-title":"Macromolecules"},{"issue":"5","key":"2026081416133167700_cit50","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1021\/acs.macromol.8b02659","article-title":"Influence\nof Chain Primary Structure and Topology (Branching)\non Crystallization and Thermal Properties: The Case of Polysulfides","volume":"52","author":"Perez-Camargo","year":"2019","journal-title":"Macromolecules"},{"issue":"7","key":"2026081416133167700_cit51","doi-asserted-by":"publisher","first-page":"6872","DOI":"10.1021\/acsnano.5b02937","article-title":"Crystalline\nOligo\u00ad(ethylene sulfide) Domains Define Highly Stable Supramolecular\nBlock Copolymer Assemblies","volume":"9","author":"Brubaker","year":"2015","journal-title":"ACS Nano"},{"issue":"7","key":"2026081416133167700_cit52","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/pat.3524","article-title":"Tuning loading and release by modification\nof micelle core crystallinity and preparation","volume":"26","author":"Glavas","year":"2015","journal-title":"Polym. Adv. Technol."},{"issue":"1","key":"2026081416133167700_cit53","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ijpharm.2009.04.046","article-title":"Influence\nof nanocarrier type and\nsize on skin delivery of hydrophilic agents","volume":"377","author":"Ku\u0308chler","year":"2009","journal-title":"Int. J. Pharm."},{"issue":"1","key":"2026081416133167700_cit54","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s00280-007-0458-z","article-title":"Pharmacometrics\nand delivery of novel nanoformulated PEG-b-poly\u00ad(epsilon-caprolactone)\nmicelles of rapamycin","volume":"61","author":"Yanez","year":"2007","journal-title":"Cancer Chemother. Pharmacol."},{"issue":"38","key":"2026081416133167700_cit55","doi-asserted-by":"publisher","first-page":"15758","DOI":"10.1021\/ja303372u","article-title":"Biocompatible\nPolymeric Nanoparticles Degrade and Release Cargo in Response to Biologically\nRelevant Levels of Hydrogen Peroxide","volume":"134","author":"de\nGracia Lux","year":"2012","journal-title":"J. Am.\nChem. Soc."},{"issue":"1","key":"2026081416133167700_cit56","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/jcp.21283","article-title":"High extracellular\ninorganic phosphate concentration inhibits RANK-RANKL signaling in\nosteoclastlike cells","volume":"215","author":"Mozar","year":"2008","journal-title":"J. Cell. Physiol."},{"issue":"10","key":"2026081416133167700_cit57","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1359\/jbmr.2001.16.10.1787","article-title":"Transforming\ngrowth factor beta affects osteoclast differentiation via direct and\nindirect actions","volume":"16","author":"Quinn","year":"2001","journal-title":"J. Bone Miner. Res."},{"issue":"1","key":"2026081416133167700_cit58","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.bone.2003.08.008","article-title":"Transforming\ngrowth factor-beta induces osteoclast formation in the absence of\nRANKL","volume":"34","author":"Itonaga","year":"2004","journal-title":"Bone"},{"issue":"6","key":"2026081416133167700_cit59","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1021\/bm070085x","article-title":"PEG-SS-PPS:\nReduction-sensitive disulfide\nblock copolymer vesicles for intracellular drug delivery","volume":"8","author":"Cerritelli","year":"2007","journal-title":"Biomacromolecules"},{"issue":"7","key":"2026081416133167700_cit60","doi-asserted-by":"publisher","first-page":"3429","DOI":"10.1021\/ma902443j","article-title":"Assessing the Role\nof Poly\u00ad(ethylehe glycol-bl-propylene sulfide) (PEG-PPS) Block Copolymers\nin the Preparation of Carbon Nanotube Biocompatible Dispersions","volume":"43","author":"Di\nMeo","year":"2010","journal-title":"Macromolecules"},{"issue":"12","key":"2026081416133167700_cit61","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1016\/j.biomaterials.2007.12.035","article-title":"Functionalization\nof polysulfide nanoparticles and their performance as circulating\ncarriers","volume":"29","author":"Rehor","year":"2008","journal-title":"Biomaterials"},{"key":"2026081416133167700_cit62","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13104-015-1000-8","article-title":"Limitations of the\n3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)\nassay when compared to three commonly used cell enumeration assays","volume":"8","author":"van\nTonder","year":"2015","journal-title":"BMC Res. Notes"},{"issue":"1","key":"2026081416133167700_cit63","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1038\/s41598-018-19930-w","article-title":"Mitochondrial biogenesis and metabolic hyperactivation\nlimits the application of MTT assay in the estimation of radiation\ninduced growth inhibition","volume":"8","author":"Rai","year":"2018","journal-title":"Sci. Rep."},{"issue":"3","key":"2026081416133167700_cit64","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nm.1910","article-title":"Coordination of PGC-1\u03b2 and\niron uptake in mitochondrial biogenesis and osteoclast activation","volume":"15","author":"Ishii","year":"2009","journal-title":"Nat. Med."},{"issue":"5","key":"2026081416133167700_cit65","doi-asserted-by":"publisher","first-page":"6605","DOI":"10.3892\/mmr.2018.8698","article-title":"TNF-alpha\nand RANKL promote osteoclastogenesis by upregulating RANK via the\nNF-kappa B pathway","volume":"17","author":"Luo","year":"2018","journal-title":"Mol. Med. Rep."}],"container-title":["Biomacromolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.biomac.9b01348","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/21\/2\/305\/5925417\/bm9b01348.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/21\/2\/305\/5925417\/bm9b01348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:23:49Z","timestamp":1786739029000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article\/21\/2\/305\/591616\/Tandem-Nanomedicine-Approach-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,3]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,12,3]]},"published-print":{"date-parts":[[2020,2,10]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.biomac.9b01348","relation":{},"ISSN":["1525-7797","1526-4602"],"issn-type":[{"value":"1525-7797","type":"print"},{"value":"1526-4602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,3]]}}}