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A novel nano delivery system targeting different stages of osteoclasts
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.ORCID iD: 0000-0001-7257-5522
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2022 (English)In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 10, no 7, p. 1821-1830Article in journal (Refereed) Published
Abstract [en]

Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist. Therefore, we designed two dual-targeting nanoparticles to target OCs at different functional stages. Using the calcitonin gene-related peptide receptor (CGRPR), which OC precursors highly express, and specific TRAPpeptides screened in the bone resorption lacuna, where mature OCs function, respectively, two types of dual-targeted nanoparticles were constructed. Afterwards, nanoparticles were grafted with hyaluronic acid (HA), which specifically binds to CD44 on the surface of the OCs. In vivo and in vitro experiments show that both nanoparticles have noticeable targeting effects on OCs. This suggests that dual-targeting nanoparticles designed for different functional periods of OC can be well targeted to the corresponding OC, and further promote the more precise delivery of drugs used to treat OP. 

Place, publisher, year, edition, pages
Royal Society of Chemistry (RSC) , 2022. Vol. 10, no 7, p. 1821-1830
Keywords [en]
Bone, Controlled drug delivery, Hyaluronic acid, Targeted drug delivery, Calcitonin gene-related peptides, Developmental stage, Different stages, Drug targets, Functional stages, Multiple process, Nano-delivery systems, Osteoclast precursor, Peptide receptor, Targeted delivery systems, Nanoparticles, acid phosphatase tartrate resistant isoenzyme, alkaline phosphatase, calcitonin, calcitonin gene related peptide, calcitonin gene related peptide receptor, calcitonin receptor like receptor, cathepsin K, colony stimulating factor 1, Hermes antigen, hyaluronic acid binding protein, layilin, membrane protein, nanoparticle, osteoclast differentiation factor, rhodamine 6G, scleroprotein, toll like receptor 4, unclassified drug, animal cell, animal experiment, animal tissue, Article, bone tissue, controlled study, drug delivery system, in vitro study, in vivo study, mouse, nanotechnology, newborn, nonhuman, osteoclast, osteolysis, osteoporosis, protein expression, human, metabolism, monocyte, Bone Resorption, Humans, Monocytes, Nanoparticle Drug Delivery System, Osteoclasts
National Category
Basic Medicine
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URN: urn:nbn:se:kth:diva-322401DOI: 10.1039/d2bm00076hISI: 000764257000001PubMedID: 35244664Scopus ID: 2-s2.0-85127062939OAI: oai:DiVA.org:kth-322401DiVA, id: diva2:1718919
Note

Correction in DOI 10.1039/d4bm90069c

QC 20241120

Available from: 2022-12-14 Created: 2022-12-14 Last updated: 2024-11-20Bibliographically approved

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Yan, Hongji

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