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Bone tumor-homing nanotherapeutics for prolonged retention in tumor microenvironment and facilitated apoptotic process via mevalonate pathway inhibition
DC Field | Value | Language |
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dc.contributor.author | Kang, Nae-Won | - |
dc.contributor.author | Visetvichaporn, Voradanu | - |
dc.contributor.author | Nguyen, Duy-Thuc | - |
dc.contributor.author | Shin, Eun Kyung | - |
dc.contributor.author | Kim, Dahan | - |
dc.contributor.author | Kim, Min-Jae | - |
dc.contributor.author | Yoo, So-Yeol | - |
dc.contributor.author | Lee, Jae-Young | - |
dc.contributor.author | Kim, Dae-Duk | - |
dc.date.accessioned | 2024-04-26T00:23:50Z | - |
dc.date.available | 2024-04-26T00:23:50Z | - |
dc.date.created | 2023-04-06 | - |
dc.date.issued | 2023-04 | - |
dc.identifier.citation | Materials Today Bio, Vol.19, p. 100591 | - |
dc.identifier.issn | 2590-0064 | - |
dc.identifier.uri | https://hdl.handle.net/10371/199460 | - |
dc.description.abstract | Bone malignancy features a mineralized extracellular matrix primarily composed of hydroxyapatite, which in-terferes with the distribution and activity of antineoplastic agents. Herein, we report bone tumor-homing poly-meric nanotherapeutics consisting of alendronate-decorated chondroitin sulfate A-graft-poly(lactide-co-glycolide) and doxorubicin (DOX), named PLCSA-AD, which displayed a prolonged retention profile in the tumor micro -environment and augmented therapeutic efficacy via inhibition of the mevalonate pathway. PLCSA-AD exhibited a 1.72-fold lower IC50 value than free DOX and a higher affinity for hydroxyapatite than PLCSA in HOS/MNNG cell-based 2D bone tumor-mimicking models. The inhibition of the mevalonate pathway by PLCSA-AD in tumor cells was verified by investigating the cytosolic fraction of unprenylated proteins, where blank PLCSA-AD significantly increased the expression of cytosolic Ras and RhoA without changing their total cellular amounts. In a bone tumor-mimicking xenografted mouse model, AD-decorated nanotherapeutics significantly increased tumor accumulation (1.73-fold) compared with PLCSA, and higher adsorption to hydroxyapatites was observed in the histological analysis of the tumor. As a result, inhibition of the mevalonate pathway and improvement in tumor accumulation led to markedly enhanced therapeutic efficacy in vivo, suggesting that PLCSA-AD could be promising nanotherapeutics for bone tumor treatment. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier | - |
dc.title | Bone tumor-homing nanotherapeutics for prolonged retention in tumor microenvironment and facilitated apoptotic process via mevalonate pathway inhibition | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.mtbio.2023.100591 | - |
dc.citation.journaltitle | Materials Today Bio | - |
dc.identifier.wosid | 000949451200001 | - |
dc.identifier.scopusid | 2-s2.0-85148696668 | - |
dc.citation.startpage | 100591 | - |
dc.citation.volume | 19 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Lee, Jae-Young | - |
dc.contributor.affiliatedAuthor | Kim, Dae-Duk | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CHONDROITIN SULFATE | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | ERK | - |
dc.subject.keywordPlus | BISPHOSPHONATES | - |
dc.subject.keywordPlus | PRENYLATION | - |
dc.subject.keywordPlus | DOXORUBICIN | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | NANOPARTICLES | - |
dc.subject.keywordPlus | OSTEOSARCOMA | - |
dc.subject.keywordAuthor | Bone tumors | - |
dc.subject.keywordAuthor | Alendronate | - |
dc.subject.keywordAuthor | Mevalonate pathway inhibition | - |
dc.subject.keywordAuthor | Hydroxyapatites | - |
dc.subject.keywordAuthor | Tumor distribution | - |
dc.subject.keywordAuthor | Apoptosis | - |
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