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The present study is aimed at designing PEGylated\u00a0nanoliposomal doxorubicin (PLD) conjugated with peptides targeting TREM2 for glioma\u2010targeting therapy. The specific peptides are designed with the Rosetta Peptiderive Protocol. Schrodinger's peptide\u2010specific version of Glide is used for molecular docking.\u00a0PLD modified with peptides (peptide\u2010PLD) are engineered and prepared. Cell cycle, apoptosis, cell invasion and migration, cell viability, and colony\u2010formation assays are performed to analyze glioma cell functions. The anti\u2010tumor effects of peptide\u2010PLD are validated in an intracranial U87\u2010MG cells orthotopic glioma model. The targeting peptides HLRKLRKR and LRKLRLRL showed specific affinity for TREM2 and better cellular uptake in U87\u2010MG cells. PLD with peptide modification demonstrated stable doxorubicin loading, small sizes (&lt;60\u00a0nm), and enrichment in the mouse brain. Peptide\u2010PLD treatment inhibited the Akt\/GSK3<jats:italic>\u03b2<\/jats:italic>\/<jats:italic>\u03b2<\/jats:italic>\u2010catenin pathway, thereby inhibiting cell invasion and migration, and colony\u2010forming ability in U87\u2010MG cells. The peptide modification of PLD achieved better suppression of glioma development than PLD.\u00a0Overall, TREM2\u2010targeting peptides are successfully designed, and peptide\u2010PLD served as a potent drug delivery carrier for glioma\u2010targeting therapy.<\/jats:p>","DOI":"10.1002\/adhm.202403096","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:24:04Z","timestamp":1734927844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PEGylated Nanoliposomal Doxorubicin Conjugated with Specific TREM2 Peptides for Glioma\u2010Targeting Therapy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9424-8247","authenticated-orcid":false,"given":"Hongyan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medical Physics Institute of Modern Physics Chinese Academy of Sciences  Lanzhou 730000 China"},{"name":"Gansu Provincial Isotope Laboratory  Lanzhou 730300 China"},{"name":"Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine  Lanzhou 730000 China"},{"name":"School of Nuclear Science and Technology University of Chinese Academy of Sciences  Beijing 101408 China"},{"name":"Advanced Energy Science and Technology Guangdong Laboratory  Huizhou 516029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duling","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Physics Institute of Modern Physics Chinese Academy of Sciences  Lanzhou 730000 China"},{"name":"Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine  Lanzhou 730000 China"},{"name":"School of Nuclear Science and Technology University of Chinese Academy of Sciences  Beijing 101408 China"},{"name":"Advanced Energy Science and Technology Guangdong Laboratory  Huizhou 516029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; Laboratory of Clinical Nuclear Medicine West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Physics Institute of Modern Physics Chinese Academy of Sciences  Lanzhou 730000 China"},{"name":"Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine  Lanzhou 730000 China"},{"name":"School of Nuclear Science and Technology University of Chinese Academy of Sciences  Beijing 101408 China"},{"name":"Advanced Energy Science and Technology Guangdong Laboratory  Huizhou 516029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitong","family":"Bing","sequence":"additional","affiliation":[{"name":"Department of Computational Physics Institute of Modern Physics Chinese Academy of Sciences  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Physics Institute of Modern Physics Chinese Academy of Sciences  Lanzhou 730000 China"},{"name":"Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine  Lanzhou 730000 China"},{"name":"School of Nuclear Science and Technology Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113510"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2016.1192470"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2015.0580"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01511-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1180943"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199700544-00005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.02.026"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158708"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2022.124387"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.004"},{"key":"e_1_2_9_11_1","first-page":"801","volume":"24792","author":"Park M. 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