Show simple item record

dc.contributor.authorMatus, María Francisca
dc.contributor.authorMalola, Sami
dc.contributor.authorHäkkinen, Hannu
dc.date.accessioned2021-07-20T07:15:52Z
dc.date.available2021-07-20T07:15:52Z
dc.date.issued2021
dc.identifier.citationMatus, M. F., Malola, S., & Häkkinen, H. (2021). Ligand Ratio Plays a Critical Role in the Design of Optimal Multifunctional Gold Nanoclusters for Targeted Gastric Cancer Therapy. <i>ACS Nanoscience Au</i>, <i>Early online</i>. <a href="https://doi.org/10.1021/acsnanoscienceau.1c00008" target="_blank">https://doi.org/10.1021/acsnanoscienceau.1c00008</a>
dc.identifier.otherCONVID_99047313
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/77190
dc.description.abstractNanodrug delivery systems (NDDSs) based on water-soluble and atomically precise gold nanoclusters (AuNCs) are under the spotlight due to their great potential in cancer theranostics. Gastric cancer (GC) is one of the most aggressive cancers with a low early diagnosis rate, with drug therapy being the primary means to overcome its increasing incidence. In this work, we designed and characterized a set of 28 targeted nanosystems based on Au144(p-MBA)60 (p-MBA = para-mercaptobenzoic acid) nanocluster to be potentially employed as combination therapy in GC treatment. The proposed multifunctional AuNCs are functionalized with cytotoxic drugs (5-fluorouracil and epirubicin) or inhibitors of different signaling pathways (phosphatidylinositol 3-kinases (PI3K)/protein kinase B (Akt)/mammalian target of the rapamycin (mTOR), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF)) and RGD peptides as targeting ligands, and we studied the role of ligand ratio in their optimal structural conformation using peptide–protein docking and all-atom molecular dynamics (MD) simulations. The results reveal that the peptide/drug ratio is a crucial factor influencing the potential targeting ability of the nanosystem. The most convenient features were observed when the peptide amount was favored over the drug in most cases; however, we demonstrated that the system composition and the intermolecular interactions on the ligand shell are crucial for achieving the desired effect. This approach helps guide the experimental stage, providing essential information on the size and composition of the nanosystem at the atomic level for ligand tuning in order to increase the desired properties.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofseriesACS Nanoscience Au
dc.rightsCC BY 4.0
dc.titleLigand Ratio Plays a Critical Role in the Design of Optimal Multifunctional Gold Nanoclusters for Targeted Gastric Cancer Therapy
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202107204364
dc.contributor.laitosFysiikan laitosfi
dc.contributor.laitosDepartment of Physicsen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn2694-2496
dc.relation.volumeEarly online
dc.type.versionpublishedVersion
dc.rights.copyright© The Authors. Published by American Chemical Society
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber319208
dc.relation.grantnumber292352
dc.subject.ysolääkehoito
dc.subject.ysonanohiukkaset
dc.subject.ysomahasyöpä
dc.subject.ysosyöpätaudit
dc.subject.ysosyöpähoidot
dc.subject.ysonanorakenteet
dc.subject.ysokulta
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p10851
jyx.subject.urihttp://www.yso.fi/onto/yso/p23451
jyx.subject.urihttp://www.yso.fi/onto/yso/p6111
jyx.subject.urihttp://www.yso.fi/onto/yso/p678
jyx.subject.urihttp://www.yso.fi/onto/yso/p27422
jyx.subject.urihttp://www.yso.fi/onto/yso/p25315
jyx.subject.urihttp://www.yso.fi/onto/yso/p19016
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1021/acsnanoscienceau.1c00008
dc.relation.funderSuomen Akatemiafi
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiaprofessorin tutkimuskulut, SAfi
jyx.fundingprogramAkatemiaprofessorin tehtävä, SAfi
jyx.fundingprogramResearch costs of Academy Professor, AoFen
jyx.fundingprogramResearch post as Academy Professor, AoFen
jyx.fundinginformationThis work was supported by the Academy of Finland (grants 292352, 319208 and HH’s Academy Professorship). The computations were done at the CSC computing center in Finland (Grand Challenge Project NanoGaC) and by using the Finnish Computing Competence Infrastructure (FCCI; persistent identifier urn:nbn:fi:research-infras-2016072533).


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

CC BY 4.0
Except where otherwise noted, this item's license is described as CC BY 4.0