Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy

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dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorFigueiredo, Patrícia
dc.contributor.authorLepland, Anni
dc.contributor.authorScodeller, Pablo
dc.contributor.authorFontana, Flavia
dc.contributor.authorTorrieri, Giulia
dc.contributor.authorTiboni, Mattia
dc.contributor.authorShahbazi, Mohammad Ali
dc.contributor.authorCasettari, Luca
dc.contributor.authorKostiainen, Mauri A.
dc.contributor.authorHirvonen, Jouni
dc.contributor.authorTeesalu, Tambet
dc.contributor.authorSantos, Hélder A.
dc.contributor.departmentUniversity of Helsinki
dc.contributor.departmentUniversity of Tartu
dc.contributor.departmentUniversity of Urbino
dc.contributor.departmentBiohybrid Materials
dc.contributor.departmentDepartment of Bioproducts and Biosystemsen
dc.date.accessioned2021-09-15T06:39:59Z
dc.date.available2021-09-15T06:39:59Z
dc.date.embargoinfo:eu-repo/date/embargoEnd/2022-09-24
dc.date.issued2020-10-02
dc.description.abstractNanomedicines represent innovative and promising alternative technologies to improve the therapeutic effects of different drugs for cancer ablation. Targeting M2-like tumor-associated macrophages (TAMs) has emerged as a favorable therapeutic approach to fight against cancer through the modulation of the tumor microenvironment. However, the immunomodulatory molecules used for this purpose present side effects upon systemic administration, which limits their clinical translation. Here, the biocompatible lignin polymer is used to prepare lignin nanoparticles (LNPs) that carry a dual agonist of the toll-like receptors TLR7/8 (resiquimod, R848). These LNPs are targeted to the CD206-positive M2-like TAMs using the “mUNO” peptide, in order to revert their pro-tumor phenotype into anti-tumor M1-like macrophages in the tumor microenvironment of an aggressive triple-negative in vivo model of breast cancer. Overall, we show that targeting the resiquimod (R848)-loaded LNPs to the M2-like macrophages, using very low dosesof R848, induces a profound shift in the immune cells in the tumor microenvironment towards an anti-tumor immune state, by increasing the representation of M1-like macrophages, cytotoxic T cells, and activated dendritic cells. This effect consequently enhances the anticancer effect of the vinblastine (Vin) when co-administered with R848-loaded LNPs.en
dc.description.versionPeer revieweden
dc.format.extent13
dc.identifier.citationFigueiredo , P , Lepland , A , Scodeller , P , Fontana , F , Torrieri , G , Tiboni , M , Shahbazi , M A , Casettari , L , Kostiainen , M A , Hirvonen , J , Teesalu , T & Santos , H A 2020 , ' Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy ' , Acta Biomaterialia . https://doi.org/10.1016/j.actbio.2020.09.038en
dc.identifier.doi10.1016/j.actbio.2020.09.038
dc.identifier.issn1742-7061
dc.identifier.otherPURE UUID: 4cf603cf-5f89-4bd9-8255-ccb6b8cb88ee
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/4cf603cf-5f89-4bd9-8255-ccb6b8cb88ee
dc.identifier.otherPURE LINK: http://www.scopus.com/inward/record.url?scp=85092252178&partnerID=8YFLogxK
dc.identifier.otherPURE LINK: https://researchportal.helsinki.fi/fi/publications/peptide-guided-resiquimod-loaded-lignin-nanoparticles-convert-tum
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/109935
dc.identifier.urnURN:NBN:fi:aalto-202109159158
dc.language.isoenen
dc.publisherElsevier BV
dc.relation.ispartofseriesActa Biomaterialiaen
dc.rightsopenAccessen
dc.subject.keywordlignin nanoparticles
dc.subject.keywordmacrophage repolarization
dc.subject.keywordmannose receptor
dc.subject.keywordmUNO
dc.subject.keywordresiquimod
dc.titlePeptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapyen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
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[article-cris] Kemian tekniikan korkeakoulu / CHEM