{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xiao B"],"funding":["NIA NIH HHS","Orthopaedic Trauma Association","National Institutes of Health","NIAMS NIH HHS","Orthopaedic Research and Education Foundation","NIH HHS","National Science Foundation"],"pagination":["e2305336"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922143"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(7)"],"pubmed_abstract":["Despite decades of progress, developing minimally invasive bone-specific drug delivery systems (DDS) to improve fracture healing remains a significant clinical challenge. To address this critical therapeutic need, nanoparticle (NP) DDS comprised of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) functionalized with a peptide that targets tartrate-resistant acid phosphatase (TRAP) and achieves preferential fracture accumulation has been developed. The delivery of AR28, a glycogen synthase kinase-3 beta (GSK3β) inhibitor, via the TRAP binding peptide-NP (TBP-NP) expedites fracture healing. Interestingly, however, NPs are predominantly taken up by fracture-associated macrophages rather than cells typically associated with fracture healing. Therefore, the underlying mechanism of healing via TBP-NP is comprehensively investigated herein. TBP-NP<sub>AR28</sub> promotes M2 macrophage polarization and enhances osteogenesis in preosteoblast-macrophage co-cultures in vitro. Longitudinal analysis of TBP-NP<sub>AR28</sub> -mediated fracture healing reveals distinct spatial distributions of M2 macrophages, an increased M2/M1 ratio, and upregulation of anti-inflammatory and downregulated pro-inflammatory genes compared to controls. This work demonstrates the underlying therapeutic mechanism of bone-targeted NP DDS, which leverages macrophages as druggable targets and modulates M2 macrophage polarization to enhance fracture healing, highlighting the therapeutic benefit of this approach for fractures and bone-associated diseases."],"journal":["Small (Weinheim an der Bergstrasse, Germany)"],"pubmed_title":["Bone-Targeted Nanoparticle Drug Delivery System-Mediated Macrophage Modulation for Enhanced Fracture Healing."],"pmcid":["PMC10922143"],"funding_grant_id":["CBET1450987","DMR2103553","20‐072","R21 AG072692","R01 AR064200","R21 AR081063","P30 AR06955","R01 AR056696","6272","S10 OD030302"],"pubmed_authors":["Adjei-Sowah E","Mereness J","Yan M","Liu Y","Chandrasiri I","Benoit DSW","Xiao B"],"additional_accession":[]},"is_claimable":false,"name":"Bone-Targeted Nanoparticle Drug Delivery System-Mediated Macrophage Modulation for Enhanced Fracture Healing.","description":"Despite decades of progress, developing minimally invasive bone-specific drug delivery systems (DDS) to improve fracture healing remains a significant clinical challenge. To address this critical therapeutic need, nanoparticle (NP) DDS comprised of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) functionalized with a peptide that targets tartrate-resistant acid phosphatase (TRAP) and achieves preferential fracture accumulation has been developed. The delivery of AR28, a glycogen synthase kinase-3 beta (GSK3β) inhibitor, via the TRAP binding peptide-NP (TBP-NP) expedites fracture healing. Interestingly, however, NPs are predominantly taken up by fracture-associated macrophages rather than cells typically associated with fracture healing. Therefore, the underlying mechanism of healing via TBP-NP is comprehensively investigated herein. TBP-NP<sub>AR28</sub> promotes M2 macrophage polarization and enhances osteogenesis in preosteoblast-macrophage co-cultures in vitro. Longitudinal analysis of TBP-NP<sub>AR28</sub> -mediated fracture healing reveals distinct spatial distributions of M2 macrophages, an increased M2/M1 ratio, and upregulation of anti-inflammatory and downregulated pro-inflammatory genes compared to controls. This work demonstrates the underlying therapeutic mechanism of bone-targeted NP DDS, which leverages macrophages as druggable targets and modulates M2 macrophage polarization to enhance fracture healing, highlighting the therapeutic benefit of this approach for fractures and bone-associated diseases.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-03T23:23:26.076Z","creation":"2025-04-03T23:23:26.076Z"},"accession":"S-EPMC10922143","cross_references":{"pubmed":["37797180"],"doi":["10.1002/smll.202305336"]}}