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PEGylated Nanoliposomal Doxorubicin Conjugated with Specific TREM2 Peptides for Glioma-Targeting Therapy

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机构： [1]Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. [2]Gansu Provincial Isotope Laboratory, Lanzhou, 730300, China. [3]Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, 730000, China. [4]School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 101408, China. [5]Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516029, China. [6]Department of Nuclear Medicine & Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China. [7]Department of Computational Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. [8]School of Nuclear Science and Technology, Lanzhou University, Lanzhou, 730000, China.

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关键词： drug delivery carrier glioma-targeting therapy PEGylated nanoliposomal doxorubicin target peptide

摘要：

PEGylated liposomes can deliver anti-cancer drugs to brain tumors, and achieve enhanced permeability and retention effects. Triggering receptor expressed on myeloid cells 2 (TREM2) is an excellent biomarker for precise therapy of glioma. The present study is aimed at designing PEGylated nanoliposomal doxorubicin (PLD) conjugated with peptides targeting TREM2 for glioma-targeting therapy. The specific peptides are designed with the Rosetta Peptiderive Protocol. Schrodinger's peptide-specific version of Glide is used for molecular docking. PLD modified with peptides (peptide-PLD) are engineered and prepared. Cell cycle, apoptosis, cell invasion and migration, cell viability, and colony-formation assays are performed to analyze glioma cell functions. The anti-tumor effects of peptide-PLD are validated in an intracranial U87-MG cells orthotopic glioma model. The targeting peptides HLRKLRKR and LRKLRLRL showed specific affinity for TREM2 and better cellular uptake in U87-MG cells. PLD with peptide modification demonstrated stable doxorubicin loading, small sizes (<60 nm), and enrichment in the mouse brain. Peptide-PLD treatment inhibited the Akt/GSK3β/β-catenin pathway, thereby inhibiting cell invasion and migration, and colony-forming ability in U87-MG cells. The peptide modification of PLD achieved better suppression of glioma development than PLD. Overall, TREM2-targeting peptides are successfully designed, and peptide-PLD served as a potent drug delivery carrier for glioma-targeting therapy.© 2024 Wiley‐VCH GmbH.

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大类 | 2 区

医学

小类 | 2 区工程：生物医学 2 区材料科学：生物材料 2 区纳米科技

第一作者：

第一作者机构： [1]Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. [2]Gansu Provincial Isotope Laboratory, Lanzhou, 730300, China. [3]Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, 730000, China. [4]School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 101408, China. [5]Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516029, China.

通讯作者：

通讯机构： [1]Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. [2]Gansu Provincial Isotope Laboratory, Lanzhou, 730300, China. [3]Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, 730000, China. [4]School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 101408, China. [5]Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516029, China.

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PEGylated Nanoliposomal Doxorubicin Conjugated with Specific TREM2 Peptides for Glioma-Targeting Therapy

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