ANG-Modified Liposomes Coloaded With α-Melittin and Resveratrol Induce Apoptosis and Pyroptosis in Glioblastoma Cells by Impeding Wnt/β-Catenin Signaling

文献类型： 外文期刊

第一作者： Zhang, Hai-Qian

作者： Zhang, Hai-Qian;Wang, Yan;Geng, Xiao;Dong, Mingxin;Sun, Chengbiao;Yu, Kaikai;Liu, Wensen;Liu, Ziwei;Xin, Wenwen;Xu, Ye;Xu, Na

作者机构：

关键词： alpha-Melittin; combination therapy; glioblastoma; pyroptosis; resveratrol; Wnt/beta-catenin signaling pathway

期刊名称：CNS NEUROSCIENCE & THERAPEUTICS （ 影响因子：5.0； 五年影响因子：5.8 ）

ISSN： 1755-5930

年卷期： 2025 年 31 卷 5 期

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收录情况： SCI

摘要： Main ProblemGlioblastoma (GB) is one of the most prevalent and devastating types of brain cancer for which efficient treatments are currently lacking because of limitations such as antitumor efficacy, brain delivery, tumor selectivity, and drug resistance. A promising strategy to overcome these obstacles is developing anticancer agents that can be delivered to GB tissues to inhibit tumors with low toxicity to normal brain tissue.MethodsWe developed liposomes encapsulating resveratrol (RES), a polyphenolic compound, and alpha-melittin (alpha-MEL), which is composed of melittin conjugated with an amphiphilic alpha-helical peptide at its N-terminus. RES-, alpha-MEL-, and alpha-MEL-RES-loaded liposomes (Lips) were modified with Angiopep-2 (ANG). The effects of the above liposomes on GB cells were assessed, and the possible mechanisms were analyzed.ResultsANG-modified alpha-MEL-RES-Lips treatment facilitated the passage of these agents through the blood-brain barrier (BBB), increased tumor targeting, and significantly reduced alpha-MEL-associated hemolysis. The combined management of alpha-MEL with RES impeded GB cell growth and prolonged the lifespan of GB tumor-bearing model mice. alpha-MEL-RES-Lips treatment triggered GB cell apoptosis and induced pyroptosis-associated protein expressions of gasdermin-D (GSDMD), gasdermin E (GSDME), cleaved caspase 3, and NLR family pyrin domain containing 3 (NLRP3), and inhibited epithelial-mesenchymal transition (EMT) by modulating the Wnt/beta-catenin signaling pathway.ConclusionANG-modified alpha-MEL-RES-Lips might be a potential nanosystem for GB therapy, and polyphenolic compounds combined with antimicrobial peptides may promote the induction of apoptosis, pyroptosis, and the apoptosis-pyroptosis switch in GB.

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